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As shown, sympatholytic, hypoglycemic and protective effects of intravenously given taurine (1.5 to 3.0 mmol/kg) are evident, but whether it only amplifies the already proven hyperpolarizing, anti-calcic, antioxidant (Wright et al., 1986; Huxtable, 1989), and antiapoptotic (Takahashi et al., 2003) direct effects or activates additional mechanisms is unknown. Taurine increases cell membrane sensitivity to insulin (Kulakowshi and Maturo, 1984). Oral supplementation of taurine in rats blunted age-related serum IGF-1declines (Carro et al., 2001). Because of the marked hypoglycemic effects observed in our early experience, we hypothesized that systemically administered taurine exerted its effects by acting upon the mechanisms determining the circulating insulin and/or IGF-1 levels.

The hypoglycemic effects of water, ethanolic and butanolic extracts prepared from the root of Malmea depressa (Baill) R.E. Fries. (Annonaceae) were studied in diabetic rats (streptozotocin induced). Oral application of water extracts at doses of 40 and 80 mg/kg, ethanolic (112 mg/kg) and butanolic (80 mg/kg) extracts significantly lowered the plasma glucose levels in diabetic rats within three hours. Glibenclamide and metformin were used as references and showed similar hypoglycemic effects like the extracts. The three extracts have a similar chemical composition (HPLC analysis).

In this study, three steroidal sapogenins (Δ3 diosgenin, diosgenin, and pennogenin) and the phytosterols, stigmasterol and β-sitosterol were isolated from Jamaican bitter yam, Dioscorea polygonoides. Their effects on fasting blood glucose and intestinal amylase and ATPases in streptozotocin-induced diabetic rats were studied. The diabetic rats (fed supplemented and unsupplemented diets) lost weight significantly compared to the normal group. There was a significant increase in the activity of α-amylase in the proximal region of the small intestinal mucosa of diabetic rats fed sapogenin extract or commercial diosgenin. However, this did not result in increased fasting blood glucose. Instead, supplementation of the diet with bitter yam sapogenin extract significantly decreased fasting blood glucose compared to the diabetic group. Supplementation of the diet with bitter yam sapogenin extract or commercial diosgenin significantly reduced Na+–K+-ATPase activity in all three regions compared to the diabetic control group. Commercial diosgenin supplementation resulted in a significant increase in Ca2+ ATPase activity in proximal region compared to the diabetic control and bitter yam sapogenin extract groups. The effect of bitter yam sapogenin extract or commercial diosgenin on intestinal Na+–K+-ATPase activity could account for their hypoglycemic properties. However, there was adverse effect on the body weight.

The novel gluconeogenesis inhibitor FR225659 and four related compounds were isolated from the cultured broth of a fungal strain No. 19353. These compounds inhibited the glucagon-stimulated gluconeogenesis of rat primary hepatocytes and had hypoglycemic effects in two different in vivo models.

This research had the objective to validate the effect of the plant Azadirachta indica (neem) in human blood cells in a normoglycemic medium. This hypoglycemic effect had been attributed by the communities to this plant. This research is experimental, in which the aqueous extract of the plant was used in a concentration of 6.4% m/v and from this, were prepared the following doses: 0.01 mg; 0.05 mg (low doses); 0.1 mg; 0.175 mg (medium doses); 0.7 mg and 1.4 mg (high doses); also it was used insulin Humulin R ® in different concentrations (0.1, 1, 10 nM) in order to compare both effects in a normoglycemic medium with human blood cells. The results demonstrated a hypoglycemic effect when the levels of glucose concentration went down in the normoglycemic medium in relation to the control. There was a significant effect (p

Troglitazone, an oral antidiabetic agent, has hypoglycemic effects in insulin-resistant animal models and humans. This study was conducted to evaluate its effect on left ventricular diastolic dynamics of a spontaneous diabetic (DM) rat model. Twenty DM rats and 20 age-matched nonDM rats were used, and 10 of each group were treated with troglitazone as a 0.2% food admixture for 10 weeks. At 5 and 15 weeks of age, Doppler echocardiography and M-mode echocardiography were performed. Troglitazone treatment significantly improved the left ventricular diastolic dynamics of DM rats: deceleration time (msec) of early diastolic inflow decreased significantly (treated 52 ±3 vs untreated 64 ±5, p = 0.0002), and peak velocity of early transmitral inflow (cm/sec) increased significantly (treated 96 ±7 vs untreated 86 ±8, p = 0.0216). The data suggest that troglitazone improves left ventricular diastolic dynamics of a DM rat model at prediabetic stage.

E. creticum has been used in folk medicine in Jordan as a remedy for scorpion stings in the rural areas and as a hypoglycemic agent. The hypoglycemic activity of an aquous decoction of plant arial parts ofE. creticum was tested in normoglycemic and streptozocin-hyperglycemic rats. Results indicate that those extract caused significant reductions in blood glucose concentration when given orally.

A monoclonal antibody (mAb), PS-7.6, to porcine somatotropin (pST) significantly enhanced the growth responses to pST injections in hypophysectomized (hypox) rats but could not be tested in pigs because of the large quantity of antibody required for a growth trial. Because pST inhibits the hypoglycemic effects of insulin, an insulin tolerance test procedure was established to measure pST activity in jugular-catheterized pigs. Doses of 0, 30, 100, and 300 micrograms/kg per day of pST were split and administered subcutaneously (sc) in equal portions twice daily for 2 d. After a 17-hr fast, plasma samples were obtained at 10-min intervals for 30 min before an intravenous injection of insulin (0.08 IU/kg) and then for an additional 50 min. Because pST increased fasting plasma glucose concentrations, preinsulin glucose values were used as a covariate to adjust the postinsulin concentrations. pST caused a dose-dependent increase in resistance to the insulin injection in these pigs. The areas under the curves (AUC), for plasma glucose were 22.1, 29.0, 39.0, and 47.2 mg/dl per min for the 0, 30, 100, and 300 micrograms/kg pST doses, respectively. Because different doses of pST could be detected, the PS-7.6 enhancement of pST treatment was evaluated. In the first experiment, five pigs/group each received sc injections of either vehicle, pST (75 micrograms/kg; approximately 3.0 mg/d), pST (75 micrograms/kg) + PS-7.6 at 3.75 mg/kg, or pST (75 micrograms/kg) + PS-7.6 at 15 mg/kg for 2 d before the insulin test. The pST and PS-7.6 were combined and incubated for at least 1 hr at room temperature before being injected. The injection of pST alone did not significantly change insulin tolerance activity (23.1 vs. 21.1, AUC), but insulin resistance was enhanced when this dose of pST also included PS-7.6 (27.4 and 29.5, AUC, respectively; P0.05). In a second experiment, the effects of PS-7.6 and PS-4.2, a mAb that did not potentiate the pST-stimulated growth of hypox rats, were compared. The five pigs/treatment received either vehicle, pST (75 micrograms/kg), pST (75 micrograms/kg) + PS-7.6 (3.75 mg/kg), or pST (75 micrograms/kg) + PS-4.2 (3.75 mg/kg) for 2 d. The administration of pST increased the resistance to insulin (26.7 vs. 18.8, AUC; P0.01), which was markedly potentiated by PS-7.6 (54.3, AUC, P0.001) but not affected by PS-4.2 (27.6 AUC). The injection of PS-7.6 at 7.5 mg/kg without exogenous pST did not alter the sensitivity to insulin. These results indicate that PS-7.6, but not PS-4.2, enhanced the insulin antagonistic activity of pST in swine, suggesting that an enhancement of pST-stimulated growth would also occur in PS-7.6-treated pigs.

The whole powder of Trigonella foenum graecum seeds and its extracts were tested for their hypoglycemic effect on normal and diabetic model rats. The powder, its methanol extract, and the residue remaining after methanol extraction had significant hypoglycemic effects when fed simultaneously with glucose. The water extract of the methanol extractive-free residue of the seed powder showed significant hypoglycemic activity at different prandial states. The Soluble Dietary Fibre (SDF) fraction showed no effect on the fasting blood glucose levels of nondiabetic or NIDDM model rats. However, when fed simultaneously with glucose, it showed a significant hypoglycemic effect (p < 0.05) in NIDDM model rats. Chemical analysis showed that the major constituent of the SDF is a galactomannan. The results confirm the involvement of SDF in the hypoglycemic effect of T. foenum graecum seeds. However, compound(s) other than SDF is (are) also involved in the hypoglycemic activity.

Averaged blood glucose levels were 400 mg/dl in nonfasted mice, and 250 mg/dl in fasted mice in 4 weeks after injection with streptozotocin (STZ, 150 mg/kg, i.v.). These mice were used for experiments. Hypoglycemic effects of hot water extracts (W) from Folium Mori (Mulberry leaves, Morus alba L., China and Japan) or Cortex Mori Radicis (Morus alba L., China) were observed in fasted and nonfasted STZ-induced diabetic mice at a single dose of 200 mg/kg (i.p.). The W from Folium Mori exhibited most potent hypoglycemic effects. The most potent fractions of Folium Mori and Cortex Mori Radicis were ethanol-insoluble extracts (A2). These A2 fractions demonstrated a fall in blood glucose levels of 24.6 +/- 6.0% and 60.5 +/- 9.1% at nonfasted STZ-mice, and 81.4 +/- 7.9% and 77.3 +/- 5.8% at fasted STZ-mice, respectively. The increase in glucose uptake was a mechanism of hypoglycemic actions by W and A2 of Folium Mori.

All medical care providers caring for patients with diabetes have had the midnight call from an embarrassed patient who says, “Doctor, I’ve made a mistake with my insulin and took the wrong dose. What should I do?” The answer, of course, is, “Eat something, and monitor your blood glucose level.” We can’t eliminate mistakes completely, but how can we make taking insulin safer? Millions of people take insulin injections several times a day, and with the advent of new insulin analogs and premixed insulin combinations, the potential for errors has increased. If there is any doubt about patients’ knowledge of the kinds and actions of the insulins they take, this issue should be explored, and the opportunity to teach them should be taken to help reduce the chance of future errors. Following are some of the more common types of insulin errors and some hints for ensuring the safety of patients who use insulin. Probably the most common error is when someone mixes up the dosages for two different kinds of insulin. Generally, this involves an intermediate- and a rapid-acting insulin, with the former nearly always at a higher dose than the latter. Often, patients realize their mistake immediately and can take steps to avoid severe hypoglycemia. This type of error is also suspected when patients have an unexpected low blood glucose level unrelated to their activity or food intake and outside of their usual pattern. This type of error can be disastrous when it is not realized, especially for patients who have little warning of dropping low blood glucose levels (hypoglycemic unawareness). Likewise, when the wrong dosage is taken of a 24-hour long-acting insulin (glargine [Lantus]), the hypoglycemic effects can be long-lasting indeed. However, a more common mistake …

Japanese researchers have uncovered a second mechanism by which sulfonylureas stimulate insulin production but avoid their hypoglycemic effects. One question is whether analogs targeting the mechanism could generate better results than marketed incretin analogs that work upstream.

The relative hypoglycemic effects of pulsatile versus steadily infused insulin have been examined in six normal subjects in whom pancreatic insulin output was suppressed by somatostatin-14. Soluble insulin was infused continuously overnight on one occasion and on another occasion the same quantity was given in pulses of 2-min duration with a gap of 11 min. The mean plasma glucose concentrations were lower when pulsed insulin was given [mean for the last hour: 4.66 ± 0.08 mmol/L (±SEM) versus 5.53 ± 0.06 mmol/L (±SEM) for steady infusion], diverging significantly (P < 0.05 paired t test) 7 h after the start of the study. The specific binding of 125I(A14)mono-iodo-insulin to monocytes was greater after pulsed insulin (2.9% with pulsed versus 2.4% with steadily infused insulin at tracer-only point; P < 0.02 paired t test). Thus, intravenous insulin has greater hypoglycemic effect when pulsed, possibly mediated by greater insulin receptor binding.

Polysaccharide fractions of the leaves of a number of Aloe species significantly reduced blood sugar level in mice. Activity-directed fractionation of the polysaccharide fraction from Aloe arborescens Mill. var. natalensis (Wood, et Ev.) Bgr. leaves yielded two glycans, arborans A and B, which elicited marked hypoglycemic effects in normal and alloxan-induced hyperglycemic mice.

A recently developed pharmacokinetic model of the insulin-glucose system has been used to investigate the contribution of insulin-induced suppression of endogenous glucose production (EGP) to the hypoglycemic effect of insulin in the treatment of diabetic ketoacidosis and to determine the influence of the initial degree of hyperglycemia on the course of insulin treatment. Simulations of the time course of glucose concentration in the plasma following low-dose insulin therapy indicate that the hypoglycemic action of insulin is largely due to insulin-dependent glucose utilization and that suppression of EGP, if it occurs at all, contributes little to the overall effect. Nevertheless, a particularly useful characteristic of the pharmacokinetic model of the insulin-glucose system that assumes little or no suppression of EGP is its ability to predict glucose rebound when insulin has been effectively depleted. Other simulations reveal that the initial degree of hyperglycemia has little influence on the clinical outcome of low-dose insulin treatment of diabetic ketoacidosis. According to the simulation, 0.1 (U/kg)/hr intravenous infusion of insulin will produce satisfactory control of plasma glucose concentrations within 5–8 hr, assuming initial glucose concentrations ranging from 500 to 1500 mg/dl.

A polysaccharide fraction of the Oriental crude drug “ninjin” (ginseng), Panax ginseng roots from China, significantly lowered blood sugar level in mice. Activity-guided fractionation of the fraction furnished four glycans, panaxans M, N, O and P, which exerted hypoglycemic effects in normal and alloxan-produced hyperglycemic mice.

N-(4-aminobenzenesulfonyl)-N′-butylurea (8) (glibutamide®) and several amino compounds were grafted on water soluble and non-toxic polymeric backbones, with the intention to study the influence of such a carrier on the hypoglycemic effects of the drug, covalently linked by ester and (or) amide bonds. The spacer by which the drug was fixed to the polymeric carrier contained 1 to 10 atoms. So far, the hypoglycemic effect of only one polymer (13d) was tested. It showed, however, negative results probably due to the amide bond of the drug which is difficult to split off.

1. 1. The effect of melatonin treatment (one or three injections daily) on plasma glucose levels in sham-operated and pinealectomized goldfish was examined. 2. 2. Melatonin significantly decreases blood glucose levels in sham-operated but not pinealectomized goldfish when the animals are maintained under continuous light. 3. 3. Melatonin significantly increased liver glycogen levels in both sham-operated and pinealectomized goldfish maintained under continuous light. 4. 4. The effect of melatonin on carbohydrate metabolism appears to be multifaceted as this hormones' hypoglycemie effects are pineal dependent while glycogenic effects are pineal independent.

SummaryMacerated decoction extracts of Zea styles exert consistent hypoglycemic effects in fasting rabbits provided they are administered parenterally. Repeated daily subcutaneous administration of the extract to non-fasting rabbits produces even fatal hypoglycemia. The statistical pattern of the hypoglycemic effect of Zea styles compares well with that of crystalline insulin and the distribution is of the gaussian normal curve. The concomitant toxic effects of the hypoglycemic extract, especially when administered intravenously, cannot be accounted for by its blood sugar reducing principle since we could separate the toxic effect from the blood sugar reducing effect.

The introduction of the orally active hypoglycemic agents has already had a profound effect on the therapy of diabetes. Unfortunately, despite a great deal of discussion in the literature, there is still much about these drugs which is uncertain and unsettled and, in general, information about their limitations is not so widely spread as claims for their utility. Although the modern era of interest in oral hypoglycemic agents began about 40 years ago with the association of this effect with the guanidines, it was first observed and confirmed more than 80 years ago as the result of salicylate therapy. Hypoglycemic effects have been noted after the oral administration of such unrelated materials as (1) sulfonamides and sulfonylureas (e.g., tolbutamide), (2) guanidines (e.g., synathalin A), (3) extracts of the akee plant (hypoglycin A and B), and (4) salicylates. It is also reasonable to suppose that more are on their way. The state of our knowledge of the modes of action of the several groups of orally active hypoglycemic agents based on clinical and experimental observations as well as their clinical uses, limitations, and dangers are discussed.

Capsule Gurmar is a new polyherbal Unani formulation developed by the R&D department of Hamdard Laboratories (Waqf) Bangladesh for management and treatment of diabetes. This study was aimed to investigate the chemical constituents and analgesic, antioxidant, neuropharmacological, cytotoxic, and hypoglycemic properties of the formulation using standard methods. Phytochemical tests on the hydromethanolic extract of the contents of the capsules showed the presence of carbohydrates, glycosides, saponins, steroids, flavonoids, alkaloids and tannins in the formulation. When tested by acetic acid-induced Writhing test, the extract at higher dose (400mg/kg) showed mild analgesic activity compared to standard drug Diclofenac-Na (10mg/kg). But, by Tail immersion method, the extract at the same dose showed moderate analgesic activity compared to the standard drug, Nalbuphine at 10mg/kg body weight. The Gurmar capsule extract exhibited high total antioxidant capacity (622.326 mg/g) and had high flavonoid (386.43 mg/g) and phenol (184.60 mg/g) contents. In the Hole cross and Open field tests, the extract displayed significant suppression of locomotor activity and exploratory behaviour of the mice. When subjected to Brine shrimp Lethality Bioassay, the extract was found to be significantly toxic to Brine shrimp nauplii (having L50 value of 3.16μg/ml). Glucose Tolerance Test (GTT) demonstrated quite strong hypoglycemic activity of the formulation, which significantly lowered the blood glucose level of the treated mice both at doses of 100 mg and 200mg/kg body weight. The hypoglycemic effect was comparable to that of the standard oral hypoglycemic drug, Metformin hydrochloride at the dose of 100mg/kg. These results indicate that Capsule Gurmar possesses mild analgesic, antioxidant, CNS depressant, cytotoxic, and hypoglycemic properties. Key words: capsule Gurmar; chemical constituents; pharmacological properties; hypoglycemic effects. DOI: 10.3329/sjps.v3i1.6794S. J. Pharm. Sci. 3(1): 18-27

BECAUSE of the increasing use of the sulfourea drugs in the treatment of diabetes1 2 3 it has become important to study the long-term effects of these compounds. The evidence thus far obtained suggests that after administration of a single dose of the sulfourea drugs, insulin is released into the pancreatic vein.4 The sulfourea drugs have likewise been shown to have hypoglycemic effects in the totally depancreatized animal treated with suboptimal doses of insulin.5 If the sulfourea drugs stimulate the beta cells in the islands of Langerhans of the pancreas, their prolonged administration could have deleterious effects on the islands similar to . . .

This study was carried out to investigate the hypocholesterolemic and hypoglycemic effect of four cowpea cultivars. Wistar rats were grouped and fed a high fat diet with 20% Bombay (BO), 20% MI 35 (MI), 20% Waruni (WA), 20% Dawala (DA) in comparison with 20% casein (HFD). Serum total cholesterol, non-HDL cholesterol, triacylglyceride and glucose concentrations and serum antioxidant activity were analysed. Serum lipids, glucose concentrations and serum antioxidant activity in WA fed rats were significantly lower (P < 0.05) than HFD. Therefore, raw Waruni cowpea produced significant hypolipidemic and hypoglycemic effects in Wistar rats.

An H2O extract of the American crude drug "Amerika-ninjin" (American ginseng), Panax quinquefolium roots, exhibited significant hypoglycemic activity in mice. Activity-guided fractionation of the extract led to isolation of three glycans, quinquefolans A, B, and C, which displayed hypoglycemic effects in normal and alloxan-induced hyperglycemic mice.

In 31 patients with atopic bronchial asthma in clinical remission and in 21 healthy sex- and age-matched subjects, the responses to intravenous tolbutamide (1.0 gm) and insulin (0.1 U/kg) were studied over a period of 2 hr. In response to tolbutamide, asthmatics released significantly less insulin, but their blood glucose levels did not differ from those of controls. Asthmatics also reacted to tolbutamide-induced hypoglycemia with significantly greater output of growth hormone to blood. Following intravenous injection of insulin, the recovery of the blood glucose concentrations was significantly reduced in asthmatic patients. More economical use of insulin and increased responsiveness to its hypoglycemic action, together with the well-known reduction in hypoglycemic effects of catecholamines in bronchial asthma, might explain why asthmatics rarely develop diabetes mellitus.

To assess the treatment of intentional insulin overdoses with intravenous (IV) glucose, we reviewed the records of 17 attempts in 15 patients seen during a ten-year period. The mean age of our patients was 29 +/- 9 years, and the mean overdose of insulin was 386 +/- 276 units. Eight patients were insulin-dependent diabetics and seven patients had no history of diabetes. We found that the nondiabetics were more likely to present with hypoglycemia (serum glucose less than 50 mg/dL) and develop recurrent hypoglycemia, despite oral intake and IV glucose infusion, than were diabetic patients (P less than .05, Fisher's exact test). We also found a significant relation (P less than .01) between the amount of insulin taken as a single overdose and either the total amount of IV glucose administered or the total time of IV glucose treatment until the hypoglycemic effects of excess insulin had resolved (glucose [g] = 52 + (.699) (dose U), R = .929 and time [h] = 10.5 + (.028) (dose U), R = .817). No patient sustained permanent complications from hypoglycemia. We conclude that prolonged, aggressive IV glucose infusion and serial monitoring of serum glucose levels is required in insulin overdoses. These patients may become hypoglycemic much later than predicted from the conventional duration of action of the various insulin preparations.

Teucrium polium has a folk reputation as a hypoglycemic agent. The hypoglycemic activity of an aqueous decoction of plant aerial parts was tested in normoglycemic and streptozotocin-hyperglycemic rats. Results indicate that this extract caused significant reductions in blood glucose concentration 4 h after intravenous administration and 24 h after intraperitoneal administration. This effect could be due to enhancement of peripheral metabolism of glucose rather than an increase in insulin release.

The hypoglycemic effects of a decoction and an ethanol extract of Trigenolla foenum graceum seeds on the serum glucose levels of normal and alloxan diabetic mice were studied. A single 0.5 ml oral dose of 40–80% decoctions to normal as well as alloxanized mice was followed by hypoglycemia developed over a 6-h period. Reduction in blood glucose concentration was highly significant, was maximum at 6 h and was dose-dependent. The hypoglycemia caused by the ethanol extract (200–400 mg/kg) in alloxanized mice was also dose-dependent and 200 mg/kg was comparable in effect to 200 mg/kg tolbutamide.

The hypoglycemic activity of extracts from muscles of pigs (Sus scrofa; P), chickens (Gallus domesticus; C) and mackerel (Scomber japonicus; M) was examined. P exhibited an insulin-like activity on conversion of glucose to total lipids in rat free fat cells and an insulin secretion-promoting effect on perfused rat pancreas. C showed an insulin-like activity, an insulin secretion-promoting effect and an inhibitory effect on hepatic glycogenolysis. M proved to have a weak insulin-like activity, and a weak insulin secretion-promoting effect, but its inhibitory effect on hepatic glycogenolysis was strong.After intraperioneal administration of P, C and M, the blood glucose levels decreased in both normal mice and alloxan-induced diabetic mice.

There are conflicting reports on the effect of insulin on plasma Ca concentration in rats. Low doses appear to decrease and higher doses to increase plasma Ca. Since birds are known to be very sensitive to parathyroid hormone and have resistance to the hypoglycemic effects of insulin, the effect of commercial and highly purified insulin on plasma Ca concentration was studied in 10-day-old chicks 60 min after the administration of the hormone. Both commerical bovine and purified porcine insulin provoked a dose-related elevation of plasma Ca. Although hypophosphatemia was observed with the highest dose of insulin used (0.4U), hypercalcemia was observed with 0.05 U insulin, a dose that did not modify plasma phosphate concentration. The slopes of the dose-response curves of insulin and parathyroid hormone were indistinguishable and different from that of 1 alpha-hydroxyvitamin D3. Neither propranolol nor deprivation of vitamin D altered the hypercalcemic response to insulin. Unexpectedly, propranolol (40 microgram/chick) provoked elevation of plasma Ca. It is concluded that insulin raises plasma Ca concentration in the chick by a mechanism(s) not yet elucidated.

alpha-Substituted-beta-arylpropionic acid derivatives were prepared and examined for hypolipidemic activity. The structure-activity relationship study showed that a chloro substituent at the alpha-position and an aryloxy or aralkyloxy substituent on the beta-aryl moiety was necessary for possession of substantial activity. In addition, some of these compounds showed hypolipidemic and hypoglycemic effects on diabetic mice. Among the 71 compounds prepared, ethyl 2-chloro-3-[4-(4-chlorobenzyloxy)phenyl]propionate (12) and ethyl 2-chloro-3-[4-(1-phenylethyloxy)phenyl]propionate (24) were the best with respect to activity and toxicity.

Normal and hypophysectomized rats, either in the fed or fasted state, were treated with bovine growth hormone (BGH) to determine whether the acute decline in plasma free fatty acids (FFA) and glucose in response to growth hormone (GH) administration could be modified by nutritional status and the presence of the pituitary. Both 1- and 3-mg. doses of BGH caused a plasma FFA diminution at 30 and 22 minutes, respectively, in hypophysectomized rats fasted for 24 hours. The hypolipemia observed with either dose of BGH was associated with an early fall in plasma glucose. The plasma glucose, however, did not subsequently return to normal levels during the 1-hour experimental period, as was the case with plasma FFA. At the higher dose of BGH plasma, FFA were markedly elevated above control levels at 1 hour, a condition indicative of the well-documented, secondary, hyper-lipemic response to GH treatment. The acute hypolipemic and hypoglycemic responses to BGH were not altered when hypophysectomized rats were used following a 42-hour fast. Hypophysectomized rats, which were not fasted, however, only exhibited the hypoglycemic response to BGH treatment; no alterations in plasma FFA levels were observed in these animals. Normal rats, either fed or fasted, showed neither the decline in plasma FFA nor of glucose following treatment with BGH. The time course of the acute hypolipemic and hypoglycemic effects of BGH in rats, when determined under the appropriate conditions of hypophysectomy and fasting, were further demonstrated to be functions of the preparation of BGH used.

Considerable research work has been done to improve insulin preparations in terms of controlled onset and duration of action [l-5] . However, despite the various types of insulin preparations available for therapy, it may still be of some interest to follow new ideas in this field. Thus, based on Katchalski’s work [6] and our own observations with enzymes and other biological active peptides covalentLy linked to synthetic polymers [7], we prepared a water soluble insulin-polyacrylate compound (I-PA).

The use of acid citrate dextrose (ACD) blood for exchange transfusion results in the delivery of a high glucose load because of the dextrose component of the ACD preservative. The hypoglycemic effects of the insulin response so achieved become apparent in the immediate postexchange period. It is suggested that apneic spells and/or convulsions in the initial hours following otherwise uneventful ACD exchanges may be due to this reactive hypoglycemia, an event exaggerated in infants who are hypoglycemic to begin with.