Search

Spontaneously Diabetic Torii (SDT) rat is a model of severe type 2 diabetes and its complications. These characteristics of SDT rat are very useful to research diseases; however, the slow onset of diabetes may limit the usefulness of this animal model. To solve this problem, we performed bilateral midbrain transection on SDT rats and evaluated whether hyperphagia accelerates the onset of diabetes. By severing ascending fibers from the nucleus tractus solitarius to limbic regions through ventral and dorsal tegmental regions, food consumption was significantly increased in SDT rats and the onset of diabetes was accelerated. Cumulative incidence of diabetes in midbrain transected SDT rats was 88.9% at 7 weeks after surgery (14 weeks of age), while sham operated rats was 20.0%. Increased food consumption was correlated to body weight, plasma glucose level, plasma triglyceride level, and plasma insulin level. In conclusion, the overeating caused by blocking anorexigenic signal in brain significantly accelerates the onset of diabetes in SDT rats. The early development of type 2 diabetes may accelerate microvascular complications and is considered useful in the study of the disease in SDT rats.

The objective of this paper was to determine the effect of tamsulosin use on plasma insulin status in benign prostatic hyperplasia (BPH) patients in Sokoto, Nigeria. Standard methods and procedures were used. At 2nd and 3rd months of tamsulosin use, there was a significant increase (P0.05). Plasma insulin at 4th months of the study in BPH patients (45-54 years) treated with tamsulosin revealed a significant increase (P0.05). BPH patients (aged 55-64 years) at 3rd month showed a significant increase (P0.05). In BPH patients aged 65 and above, there was no significant difference (P>0.05) in plasma insulin values from 1st through 4th month compared to baseline and other inter mean values comparisons. Plasma insulin at 0th , 1st , 2nd , 3rd and 4th months of BPH patients of different age groups treated with tamsulosin revealed no significant differences (P>0.05). This study revealed that tamsulosin use in the patients lead to significant increase in plasma insulin level (hyperinsulinemia). Careful and routine monitoring of BPH patients should be done. Patients need enough exercise activities and some drugs can be administered to alleviate elevated glucose or insulin. Keywords: Tamsulosin, hyperinsulinemia, benign prostatic hyperplasia patients, insulin resistance

We examined the prevention effect of red clover (Trifolium pratense L.) sprout on metabolic syndrome using a high-carbohydrate and high-fat diet (Western diet; WD)-induced male C57BL/6J obese model mouse. Red clover sprout-lyophilized powder (RC) contained 3.5 mg/g dry-weight of formononetin as a major phenolic compound, as analyzed by high performance liquid chromatography. Supplementation of 0.3% (w/w) RC in a WD (WD+RC) showed an anti-obesity effect and ameliorated lipid metabolism in the obese model mice. Additionally, fasting plasma glucose levels were significantly reduced in the WD+RC group. Administration of 0.1 mg/kg formononetin reduced the postprandial blood glucose level, as assessed using the oral maltose tolerance test. However, no significant formononetin intake effect was observed on the plasma insulin level. These results suggest that the formononetin contained in red clover sprout inhibits α-glucosidase and thereby contributes to reducing the postprandial blood glucose response in mice.

Objective: to detect the changes induced by STZ induced diabetes on uterine contractility and expression of connexin 43 in pregnant rat and the possible role of L carnitine to detect the role of L Carnitine in a model of diabetic pregnant rat. Method:40 female Sprague Dawley rats were subdivided into four groups; G I (NC): normal pregnant rats, G II (DI): in which rats received single i.p injection of 40 mg/kg b.wt STZ at day 1 of pregnancy, G III (DI+CAR): in which rats received STZ as above, and then at day 3 of pregnancy, diabetic pregnant rats received daily i.p L carnitine injection at a dose of 100 mg/kg b.wt till end of pregnancy, and G IV (DI+INS): in which rats received STZ as above, and then at day 3 of pregnancy, diabetic pregnant rats received daily i.p insulin injection at a dose of 1 IU/100 g b.wt (till end of pregnancy. Plasma glucose and insulin level, uterine contractility, pathological changes were assessed at the end of the experiment and scarifying of rats. Results: STZ induced DM caused significant increase in plasma glucose level, decreased plasma insulin level, impaired uterine contractility, pathological changes in diabetic group compared to normal control group. L Carnitine caused significant improvement in the studied parameters.

Background: Ascertaining Kraft dynamic insulin response patterns following a 3-h 100 g oral glucose tolerance test seems to be the most reliable method for diagnosing hyperinsulinaemia. However, this test may be too resource-intensive for standard clinical use. Aim: This study aims to see if Kraft patterns can be accurately predicted using fewer blood samples with sensitivity and specificity analyses. Setting: St Joseph Hospital, Chicago, Illinois, United States and Human Potential Centre, Auckland University of technology, Auckland, New Zealand. Method: We analysed the results of 4185 men and women with a normal glucose tolerance, who had a 100 g oral glucose tolerance test with Kraft pattern analysis. Participants were dichotomised into normal–low insulin tolerance (Kraft I or V patterns) or hyperinsulinaemia (Kraft IIA–IV patterns). Sensitivity and specificity analysis was applied to available variables (including age, body mass index, fasting insulin or glucose) both individually and in combination. Results: Out of a maximal combined sensitivity and specificity score of 2.0, 2-h insulin level > 45 µU/mL attained the highest score (1.80). Two-hour insulin also attained the highest sensitivity (> 30 µU/mL, 0.98) and the highest specificity (> 50 µU/mL, 0.99) scores. Combining the 2-h insulin with other variables reduced the sensitivity and/or specificity. Dynamic measures had a better combined sensitivity and specificity compared to fasting or anthropological measures. Conclusion: People with a 2-h plasma insulin level < 30 µU/mL are unlikely to be hyperinsulinaemic. Given that first-line treatment is lifestyle modification, we recommend that a 2-h plasma insulin level > 30 µU/mL following a 100 g oral glucose tolerance test be used to identify the hyperinsulinaemic individual.

Objective: To determine the effects of supervised structured aerobic exercise training (SSAET) program on fasting blood glucose level (FBGL), plasma insulin level (PIL), glycemic control (GC), and insulin resistance (IR) in type 2 diabetes mellitus (T2DM). Methods: Riphah Rehabilitation and Research Centre (RRRC) was the clinical setting for this randomized controlled trial, located at Pakistan Railways General Hospital (PRGH), Rawalpindi, Pakistan. Study duration was 18 months from January 1, 2015 to June 30, 2016. Patients of both genders ranging 40-70 years of age with at least one year of history of T2DM were considered eligible according to WHO criteria, while patients with other chronic diseases, history of smoking, regular exercise and diet plan were excluded. Cohorts of 195 patients were screened out of whom 120 fulfilled the inclusion criteria. Amongst them 102 agreed to participate and were assigned to experimental (n=51) and control (n=51) groups. Experimental group underwent SSAET program, routine medication and dietary plan, whereas the control group received routine medication and dietary plan, while both group received treatment for 25 weeks. The blood samples were taken at baseline and on the completion of 25 weeks. The investigation of fasting blood glucose level, plasma insulin level, and glycemic control was conducted to calculate IR. Results: Patients with T2DM in experimental group (n=51) treated with SSAET program, routine medication and dietary plan significantly improved FBGL (pre-mean= 276.41±25.31, post-mean=250.07±28.23), PIL (pre-mean=13.66±5.31, post-mean=8.91±3.83), GC (pre-mean=8.31±1.79, post-mean 7.28±1.43), and IR (pre-mean=64.95±27.26, post-mean 37.97±15.58), as compared with patients in control group treated with routine medication and dietary plan in whom deteriorations were noted in FBGL (pre-mean=268.19±22.48, post-mean=281.41±31.30), PIL(pre-mean=14.14±5.48, post-mean=14.85±5.27) GC (pre-mean=8.15±1.74, post-mean=8.20±1.44, and IR (pre-mean=64.49±23.63. post-mean=70.79 ±23.30). Statistically at the baseline the results were not significant (p>0.05), but at the completion of 25 weeks intervention all the variable showed significant results (p

5,7-Dihydroxytryptamine (5,7-DHT) is a neurotoxin which causes the depletion of serotonin. Moreover, the serotonergic system is the regulator of the blood glucose level. However, the role of centrally located serotonergic system in blood glucose regulation after D-glucose feed and immobilization (IMO) stress was not clearly characterized yet. Thus the present study was designed to examine the effect of 5,7-DHT administered intracerebroventricularly (i.c.v.) or intrathecally (i.t.) on the blood glucose level in D-glucose-fed and immobilization stress models. Mice were pretreated once i.c.v. or i.t. with 5,7-DHT (from 10 to 40 µg) for 3 days and D-glucose (2 g/kg) was fed orally. The blood glucose level was measured at 0, 30, 60 and 120 min after D-glucose feeding and immobilization stress initiation. We found that i.c.v. or i.t. pretreatment with 5,7-DHT attenuated the blood glucose level in both animal models. D-glucose feeding causes an increase in plasma insulin level, whereas the plasma cortico...

Background: Oxidative stress induced by hyperglycaemia plays a crucial role in the development of diabetic complications and metformin is commonly used in treating diabetes mellitus (DM). The aim of this study was to investigate whether metformin at the dose of 100 mg/kg/day could ameliorate oxidative stress and improve plasma insulin level in streptozotocin-induced diabetic rats.Methods: Twenty one rats (8-10 week old; weighing 190-220 g) were assigned into three groups (n=7 rats per group) i.e. non-DM, DM and DM+metformin (100 mg/kg/day metformin) groups. DM was induced using streptozotocin (60 mg/kg) intraperitoneally and treatments were given daily by oral gavage for four weeks. The levels of plasma biomarkers such as fasting blood glucose, oxidant-antioxidant markers and insulin levels were analysed.Results: Fasting blood glucose, malonyldehyde and protein carbonyls levels were significantly higher while insulin, total antioxidant capacity, catalase and glutathione peroxidase levels were significantly lower in DM group compared to non-DM group. The levels of fasting blood glucose, malonyldehyde and protein carbonyls were significantly lower while levels of total antioxidant capacity, catalase and insulin were significantly higher in DM+metformin group compared to DM group.Conclusion: This study may suggest that metformin at the dose of 100 mg/kg/day for 4 weeks reduces oxidative stress status and improves plasma insulin level in streptozotocin-induced diabetic rats possibly through its antihyperglycaemic action.

Male patients with idiopathic hypogonadotropic hypogonadism (IHH) characterized with low serum testosterone(T) might have higher risks of diabetes and coronary heart disease partly due to the high level of plasma insulin. Low serum T might also affect the body fat mass(BFM) in patients with IHH. However, the relationship between BFM and plasma insulin level in IHH patients has not been clearly clarified. A total of 22 patients who were admitted to our hospital with IHH and normal glucose tolerance(NGT) confirmed by oral glucose tolerance test and 10 healthy subjects as controls were enrolled into our study. Glucose, insulin, serum T levels, HOMA-IR, HOMA-B and percentage of BFM were determined. When compared with controls subjects, patients with IHH had significantly lower T concentrations(1.80nmol/L vs. 19.82nmol/L, P BFM was an independent factor of plasma insulin level in IHH patients with NGT. Disclosure X. Yang: None. Q. Lin: None. X. Hu: None. W. Xu: None. H.R. Deng: None.

The long-term administration of insulin requires the development of new delivery routes. Using a base developed in-house, called HAMIN®, an insulin suppository containing 100 units (U) of insulin was formulated. The suppository was subjected to stability testing at various temperatures and the assay value was monitored. Other physical factors such as hardness, disintegration time, thermal analysis and dissolution were also tested. The suppository released more than 80% of its drug content in 30 min, and was stable for up to 11 months at −20°C. The suppository effect was studied on 11 New Zealand white rabbits, with body weight ranging from 1.6 to 2.1 kg. The results show that there was a marked reduction in glucose content when the suppository was inserted. The average drop in glucose content was 2.7 mmol/L in 15 min from the time of insertion. The maximum drop in glucose content reached 3.9 mmol/L in 2 h. Plasma insulin level, quantified using an enzyme-linked immunosorbent assay, showed a value of more ...

The present study investigated the effect of parity on plasma insulin level around parturition in Saanen goats. On d -14, -7, 0, 3, 7, 10, and 14 from parturition, plasma glucose, NEFA, free AA, cortisol, and insulin concentrations were analyzed in 10 primiparous and 10 multiparous goats. At parturition, BW of primiparous goats was about 75% of that of multiparous ones (P < 0.001) and then their milk production was lower than that of multiparous ones (P < 0.001). At parturition, glucose increased (P < 0.01) in both primiparous and multiparous goats and then decreased (P < 0.01) on d 3 of lactation, remaining higher (P < 0.01) in primiparous than multiparous goats until the end of the study period. In both groups, free AA decreased (P < 0.01) at parturition, returning to prepartum levels (P < 0.01) on d 3 of lactation without difference between groups. Only in multiparous goats, plasma NEFA increased at parturition (P < 0.01), returning to prepartum levels on d 14 (P < 0.01). Changes in glucose and AA could have been caused by cortisol, which increased (P < 0.01) at parturition in both primiparous and multiparous goats, returning to prepartum levels (P < 0.01) on d 7 of lactation, without difference between the parity groups. In multiparous goats, insulin decreased soon after parturition (P < 0.05), remaining at low levels until the end of the study period, whereas in primiparous goats, insulin did not vary until d 14 of lactation, when it decreased (P < 0.05) also in this group. Therefore, between d 3 and 14 of lactation, insulin was higher in primiparous than multiparous goats (P < 0.05). Only in primiparous goats, at kidding, insulin was negatively correlated to BW (P < 0.01), and after parturition it was negatively correlated with milk yield (P < 0.05) and plasma NEFA (P < 0.05). We hypothesize that higher insulin levels in primiparous Saanen goats, which are still immature at their first breeding season, acted to limit both the mobilization of bodily reserves and the capture of nutrients by the lactating mammary gland, thus providing nutrients for their own physical and physiological development.

Plant-based remedies have been used to treat numerous diseases for thousands of years in various parts of the world. Azadirachta excelsa or sentang traditionally used by Malay as an agent for lowering blood glucose. The study was designed to evaluate the antidiabetic properties of this plant by measuring the plasma blood glucose level, the percentage of HbA1c and the plasma insulin level. Thirty two Sprague dawley rats were divided into four groups which received different treatments. The first and second groups served as positive and negative control were treated with saline respectively while the rats in the third group were received metformin. The fourth group was treated with ethanolic extract of A. excelsa. After 14 days of treatment, the plant extract was significantly reduced the fasting blood glucose and the concentration of HbA1c in diabetic rats by 72.89% and 6.58% respectively. The plasma insulin in diabetic rats was also significantly increased after treated with plant extract. These results suggest that the ethanolic extract of A. excelsa possess antidiabetic activity by improving the insulin secretion, with consequent decrease in the level of plasma blood glucose and HbA1c.

The antidiabetic activity of Thea sinensis was investigated in KK-Ay mice, an animal model of genetically type 2 diabetes with hyperinsulinemia. The water extract of Thea sinensis (green tea cold ext) (100 mg/kg body weight) reduced the blood glucose of KK-Ay mice 4 and 8 weeks after repeated administration and tended to decrease the plasma insulin level of KK-Ay mice under similar conditions. However, green tea cold ext did not affect blood glucose levels in normal mice. Green tea cold ext decreased blood glucose levels in an insulin tolerance test. These results suggest that the antidiabetic activity of green tea cold ext is derived, at least in part, from a decrease in plasma insulin, due to decreased insulin resistance.

The purpose of the present study was to examine the responses of plasma growth hormone (GH) and insulin-like growth factor-I (IGF-I) levels to intravenous injection of xylazine in female dairy calves. Xylazine (0.05, 0.15 and 0.30 mg/kg body wt., i.v.) injections induced a significant dose-dependent increase in plasma GH level within 30 min. After plasma GH levels reached peaks, GH concentrations began to decrease immediately and they returned to control levels 1 h after xylazine injection. Plasma IGF-I concentration tended to be suppressed by xylazine treatment. Xylazine induced a significant dose-dependent increase in plasma glucose for 3.5 to 5.5 h after the treatments. Xylazine also induced a significant decrease in plasma insulin level within 30 min after treatments. The present data suggested that xylazine stimulates GH release in cattle.

Sulfonylureas are widely used as an antidiabetic drug. In the present study, the effects of sulfonylurea administered supraspinally on immobilization stress-induced blood glucose level were studied in ICR mice. Mice were once enforced into immobilization stress for 30 min and returned to the cage. The blood glucose level was measured 30, 60, and 120 min after immobilization stress initiation. We found that intracerebroventricular (i.c.v.) injection with 30 µg of glyburide, glipizide, glimepiride or tolazamide attenuated the increased blood glucose level induced by immobilization stress. Immobilization stress causes an elevation of the blood corticosterone and insulin levels. Sulfonylureas pretreated i.c.v. caused a further elevation of the blood corticosterone level when mice were forced into the stress. In addition, sulfonylureas pretreated i.c.v. alone caused an elevation of the plasma insulin level. Furthermore, immobilization stress-induced insulin level was reduced by i.c.v. pretreated sulfonylureas. Our results suggest that lowering effect of sulfonylureas administered supraspinally against immobilization stress-induced increase of the blood glucose level appears to be primarily mediated via elevation of the plasma insulin level.

To elucidate the effect of aging and blood pressure on glucose tolerance, we examined the subjects who received 75g OGTT annually for 10 years. They were classified into 2 groups by blood pressure, and into 4 groups by age. The study group consisted of 34 cases (mean 62 years old), including 11 hypertensive (HT) and 23 normotensive (NT) control. All cases had their body weight fluctuate in less than 4 kgs. After blood pressure was measured, blood was drawn for determination of plasma glucose and insulin concentrations in each subject before 75g OGTT and 30, 60, 90, 120 minutes afterward. sigma BS and sigma IRI were defined as the sum of 5 points in BS and IRI, respectively. Insulinogenic index (I.I) was defined as deltaIRI/deltaBS in 30 min. sigma IRI/sigma BS and I.I of each year were calculated serially. They were compared between HT and NT group, and among 4 groups of age; 40s, 50s, 60s and 70s. sigma IRI/sigma BS was significantly decreased in both HT and NT groups (0.52 +/- 0.05 (mean +/- SE) to 0.29 +/- 0.04; p

Oral glucose (75 g) tolerance tests were performed on 189 urbanized Micronesians with an age range of 15 to 70 years. The subjects were divided into 6 groups on the basis of the 2 h plasma glucose and the pattern of insulin response examined. Fasting plasma insulin levels were not significantly different over the entire range of glucose tolerance. The 2 h plasma insulin levels were highest in the group with 2 h plasma glucose value of 140–199 mg/100 ml. There was a progressive fall in 2 h plasma insulin with increasing glucose intolerance, so that in the group with a 2 h plasma glucose ⩾ 400 mg/100 ml, the 2 h plasma insulin level was significantly less than that in all the other groups. Obesity was the most important factor influencing both fasting and 2 h insulin levels and no effect of corresponding plasma glucose level was demonstrated. In maturity-onset diabetes, a wide range of insulin responses may be seen and the earlier controversy regarding patterns of insulin response has arisen from equating groups of diabetic subjects with varying degrees of glucose intolerance.

Effects of l-methyl-2-(β-naphthyl)-aziridine (250059-S), which possesses characteristic tranquilizing actions, on levels of blood glucose and liver glycogen, and on adrenaline release from the adrenal gland were studied in rats. While there was no elevation of blood glucose, a decrease of liver glycogen was detected after an s.c. injection of 250059-S (5 or 25 mg/kg). Marked decrease of adrenaline content in adrenal glands was observed 2 hours after subcutaneous administration of 50 mg/kg of this compound. This result is consistent with the marked adrenaline secretion from the adrenal gland into adrenal-venous blood after injection of 25 mg/kg or more of 250059-S. In splanchnicotomized rats, however, 250059-S-induced adrenaline release was not clearly observed. Pretreatment with 250059-S prevented adrenaline-induced hyperglycemia. 250059-S, at doses of 10 and 25 mg/kg, elevated the plasma insulin level to about twice that of the control. The 250059-S-induced depletion of liver glycogen was not completely blocked by adrenal demedullation, although it completely disappeared with pretreatment with 10 mg/kg of propranolol. In conclusion, 250059-S causes hypersecretion of adrenaline from the adrenal glands through excitation of the splanchnic nerves, though it causes no elevation of blood glucose, mainly because of its direct or indirect blocking action on adrenaline hyperglycemia.

UNLABELLED Insulin binding to isolated adipocytes from 16 normal and 14 obese patients was studied. The data indicated that, as a group, adipocytes from the obese patients bound significantly less insulin than normal. However, of the 14 obese patients, 5 were not hyperinsulinemic and 4 of these 5 subjects had normal insulin binding. These subjects were also younger, and had the onset of obesity in childhood. When these five patients were separated from the original 14 obese patients, enhanced differences in insulin binding to adipocytes were observed when normals and the remaining 9 obese subjects were compared. Similar findings were obtained with isolated circulating mononuclear cells from these same patients. Presumably the five normoinsulinemic obese patients were not insulin-resistant, and, thus, the data indicate that insulin binding to adipocytes was decreased only in insulin-resistant obese patients. This conclusion was strengthened by finding a highly significant correlation (r=-0.71, p less than 0.001) between insulin binding to adipocytes and fasting plasma insulin level, while a weaker correlation (r=-0.49,p less than 0.01) existed between insulin binding and degree of obesity. Finally, when insulin binding to adipocytes and mononuclear cells from the same individual was compared, a significant positive correlation was found (r=0.53,p less than 0.01). IN CONCLUSION (a) insulin binding to adipocytes and mononuclear cells is decreased in cells from insulin-resistant obese patients; (b) a significant inverse relationship exists between fasting plasma insulin level and insulin binding to adipocytes; and (c) in obesity, events that affect insulin receptors on adipocytes similarly affect insulin receptors on mononuclear cells.

The effect of physiological dose of purified secretin on glucose-stimulated insulin secretion was studied in healthy volunteers during a continuous infusion of glucose. The intravenous injection of ten unit of secretin during the infusion of glucose caused a greater rise in plasma insulin level and a more marked decrease in blood glucose concentration than either the infusion of glucose or secretin alone did, resulting in a significant increase in the insulinogenic index. One unit of secretin has no effect on plasma insulin and glucose concentrations in the fasting or hyperglycemic state.The physiological role of secretin in regulating insulin secretion after ingestion of food was discussed.

Extract: A steady-state radioglyucose dilution technique was used to determine new glucose production in six newborn (1–4 days) and two adult dogs in the postabsorptive state, and during a 90-min glucagon infusion. Basal new glucose production rates were 2.0 and 2.2 mg/kg body weight per minute in the adults. In contrast, basal rates in the newborn were 2–4 times (4.1–7.9 mg/kg/min) the values for the adults. During glucagon-induced hyperglycemia in the adult, glucose production increased to 2.5 times the basal level, while plasma glucose concentration rose to a peak at 30 min. The newborn dog responded with only a 40% increment above basal production while glucose concentation rose continuously. The adult responded with a rise in plasma insulin level but no change was observed in the newborn. The fractional rate of glucose utilization during the glucagon-induced hyperglycemia was observed to decline in newborn dogs; no decline was observed in the adults. Glucose metabolism in the newborn differs from that in the adult dog as follows: 1) basal glucose production and utilization per unit body weight are rathter in the newborn; and 2) during glucagon-stimulated hyperglycemia the newborn adaps with less acceleration of both the production and the utilization of glucose. Speculation: If the human newborn responds similarly to the puppy, then hepatic glucose output appears to be near maximum in order to meet basal requirements for glucose. Conditions that accelerate peripheral tissue glucose uptake will, therefore, rapidly result in hypoglycemia. Conversely, a reduction in hepatic output may result in low blood glucose concentration.

The plasma insulin was measured by a radioimmunoassay method in 48 non-pregnant or pregnant women during glucose tolerance test (100 g glucose by mouth). Each of these 2 groups included non-obese, non-diabetic women, obese females and potential diabetic patients. The non-obese, non-diabetic, non-pregnant subjects showed mean plasma insulin levels of 25.2, 77.2, 57.0, 57.8 and 44.7μU/ml respectively 0, 45, 90, 135 and 180 minutes after glucose loading. The obese normoglycemic non pregnant females presented a normal fasting plasma insulin level which reaches 184.7,μU/ml 45 minutes after glucose intake. The late pregnancy (7th to 9th month) did not change the plasma insulin observed in the non-obese, non-diabetic and obese women. The non-pregnant females with potential diabetes showed a normal fasting plasma insulin with a maximum of 96.9μU/ml 90 minutes after the beginning of the test. In these patients between the 4th to the 9th month of the pregnancy, the maximum of 68.2μU/ml was only obtained 3 hours after the glucose loading.-The physio-pathological significance of these results is discussed.

Secretory responses of plasma insulin, glucagon, cortical and glucose to heat exposure (33°C, 60% RH) were investigated using Holstein calves. Plasma gluagon concentration had a significant increase, but plasma insulin, cortisol and glucose had significant decreases within 24 h following heat exposure. Concerning subsequent responses to heat exposure, plasma glucagon level maintained increased concentrations for 8 days of heat exposure. Plasma insulin level increased on and after day 4 of heat exposure. However, plasma cortisol and glucose levels maintained declined levels throughout the heat days.

Paraquat dichloride was administered (45 mg/kg i.p.) to male Sprague-Dawley rats. The rats were sacrificed at different times after treatment. Blood was collected and plasma was used for various biochemical measurements. A significant increase in creatine phosphokinase activity was obtained at 12, 24, and 48 hr after paraquat treatment. The activities of glutamic oxaloacetic transaminase (GOT) and sorbitol dehydrogenase were also consistently elevated in paraquat-treated animals but a statistically significant increase was obtained only at 48 hr for GOT. Paraquat had no effect on glutamic pyruvic transaminase activity. Paraquat caused a marked increase in blood glucose and a marked depletion of liver glycogen that lasted for at least a period of 48 hr. The plasma insulin level in paraquat-treated animals was markedly depressed as compared to saline control. Various possibilities have been discussed for the hyperglycemic and liver glycogen-depleting effects of paraquat in the rat.

Insulin resistance was studied by comparing insulin response and insulin binding in four groups of rats. Glucose metabolism in isolated fat cells from male Wistar rats weighing 340 g was less responsive to a supramaximal dose of insulin than glucose metabolism in fat cells from rats weighing 200 g. Induction of streptozotocin-diabetes in rats weighing 200 g resulted in a marked decrease in the insulin responsiveness of fat cells. Ventromedial hypothalamic lesions of 340 g rats had the opposite effect and restored the insulin responsiveness of fat cells. The responsiveness in the four groups was correlated to the rate of glucose conversion to fatty acids in fat cells. The binding of 125I-insulin was the same in both 340 and 200 g rats. The ventromedial hypothalamic lesioned rats and the diabetic rats showed, in spite of their great difference in insulin responsiveness, the highest binding of 125I-insulin to fat cells. Insulin binding was not correlated to the plasma insulin level which however was reflected in the lipoprotein lipase activity in the adipose tissue. In conclusion, these results indicate that variations in insulin responsiveness in fat cells are due to alterations in cellular metabolism rather than in insulin binding.

The effect of mazindol on insulin and glucagon secretion was studied in ventromedial hypothalamic lesioned (VMH) obese rats with hyperinsulinemia and VMH sham rats. Three weeks after the VMH or sham operation, VMH and sham rats were divided into two groups: one was fed diet containing mazindol (50 mg/kg) and the other was fed diet without mazindol. They were housed three more weeks before the experiment. Mazindol reduced significantly body weight increase and calorie intake in VMH rats, but not in sham rats. In addition, the fasting plasma insulin level and the arginine-induced insulin secretion in VMH rats treated with mazindol were significantly lower than those in the VMH rats without treatment of mazindol. On the other hand, in both in vivo and in vitro experiments, mazindol produced no significant change in the insulin secretion of sham-operated rats. These results suggest that mazindol suppresses hypersecretion of insulin in VMH rats probably through an anorectic effect and/or suppression of vagal hyperactivity.

Changes in plasma glucose and insulin concentration in response to palatinose ingestion were compared with those to sucrose in eight normal volunteers. When 50 g of palatinose was administered, the plasma glucose gradually increased to its peak of 110.9 +/- 4.9 mg/dl at 60 min after administration and maintained a plateau during the 120 min of the experiment. The peak value of plasma glucose to 50 g sucrose in the same group was 143.3 +/- 8.8 mg/dl at 30 min after administration and then the value sharply decreased to the fasting level. The cumulative increase in plasma glucose (sigma delta PG) to palatinose was significantly smaller than that to sucrose. The changes in the plasma insulin level almost paralleled those in the plasma glucose level. These results indicate that palatinose is more slowly absorbed than sucrose and therefore useful as a sweetener for diabetic patients.

The diurnal change in plasma immunoreactive insulin level of seventeen diabetic patients was studied before and after the treatment with sulfonylurea. The insulin area was calculated as an index to represent the diurnal summation of plasma insulin. The insulin area of the mild diabetic group and that of the moderately severe group were within a normal range before and after the treatment. The area decreased significantly in the mild diabetic group by the treatment, with a concomitant decrease in the blood glucose. However, the insulin area was unchanged in the moderately severe group. This result may be attributed to an increase of the sensitivity to insulin of the tissues by the treatment in mild diabetic group. In moderately severe group, the plasma free fatty acids (FFA) remained high still after the treatment and this high FFA is thought to be one of the reasons for unchanged plasma insulin level in this group.

The plasma insulin level and glucose tolerance were studied In five patients with homocystinuria. Two of them showed a marked hyperinsulinemia and a concomitant pathologic glucose tolerance, while the remaining three showed a normal glucose tolerance, two of them, however, had plasma insulin values in the upper level of the normal range. These preliminary results support the earlier hypothesis that the pancreatic islets β-cells are particularly sensitive to an imbalance in the sulfhydryl levels of the organism since homocystinurics have an increased plasma methionine level due to an inborn error of the methionine metabolism.