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Context: The global prevalence of diabetes mellitus, and in particular type 2 diabetes mellitus is increasing at an alarming rate. Risk factors for development of diabetes include obesity and advancing age., Objectives: The distribution of insulin, glucagon, somatostatin and pancreatic polypeptide in the pancreatic islets has been investigated in young and elderly type 2 Zucker diabetic fatty (ZDF) rats and age-matched Zucker lean (ZL) controls., Methods: Experiments were performed in male animals aged either 9-13 weeks or 30-34 weeks. Immunohistochemistry was used to label insulin, glucagon, somatostatin and pancreatic polypeptide in islet cells., Results: The percentage of insulin-positive cells was unaltered in young but decreased in elderly ZDF (35.5 ± 2.5%) rats compared to ZL controls (57.9 ± 1.8%). The percentage of glucagon-positive cells was increased in young ZDF (58.7 ± 3.4%) compared to ZL controls (23.4 ± 2.1%). However, in elderly rats the percentage of glucagon-positive cells declined in ZDF rats and was no longer different from ZL controls. The percentage of somatostatin-positive cells was unaltered in young and elderly ZDF rats compared to ZL controls. The percentage of pancreatic polypeptide-positive cells was unaltered in young but increased in elderly ZDF (22.0 ± 2.5%) rats compared to ZL controls (13.8 ± 1.8%)., Conclusions: The distribution of pancreatic hormones is altered to varying extents in the ZDF rat and during the normal aging process.

Context: Exercise training has long been utilized as an adjunct to pharmacotherapy in the management of diabetes., Objectives: The effects of a heavy exercise training program on the distribution of insulin, glucagon, somatostatin and pancreatic polypeptide in pancreatic islet cells of diabetic rats was investigated., Animals: Forty male Wistar rats., Design: The animals were divided into 4 groups: control sedentary, diabetic sedentary, control heavy exercise, and diabetic heavy exercise., Intervention: Diabetes was induced with a single injection of streptozotocin (60 mg/kg i.p.). The exercise program included five 60-min sessions per week, speed 18 m/min with a running belt at a 5% incline and began 1 week after the streptozotocin treatment and continued for 12 weeks., Main Outcome Measure: Immunohistochemistry was used to label insulin, glucagon, somatostatin and pancreatic polypeptide in islet cells., Results: The percentage of insulin-positive cells was significantly lower in islets from diabetic rats (24.2+/-2.3%) as compared to the controls (87.5+/-2.0%). The percentage of glucagon-positive cells was significantly higher in islets from diabetic rats (44.0+/-1.7%) as compared to the controls (34.7+/-2.1%). The percentage of pancreatic polypeptide-positive cells was also significantly higher in islets from diabetic rats (20.8+/-1.6%) as compared to the controls (12.7+/-1.8%). The percentage of somatostatin-positive cells was not significantly altered in islets from diabetic rats (28.2+/-2.0%) as compared to the controls (21.9+/-2.7%). Heavy exercise did not significantly alter insulin, glucagon, pancreatic peptide or somatostatin labeling in either diabetic or control rats., Conclusions: Alterations in the distribution of pancreatic hormones in streptozotocin-induced diabetic rats, a model of type 1 diabetes, are not improved with heavy exercise.

Objectives: The pattern of distribution of calcitonin-gene related peptide (CGRP), a neuropeptide, gamma-aminobutyric acid (GABA), a neurotransmitter and GABA-converting enzyme, glutamic acid decarboxylase (GAD) in the pancreas of diabetic patients was investigated to determine whether diabetes mellitus influences the expression of these biological transmitters., Methods: Pancreatic tissue samples retrieved, during pancreatectomy, from cancer patients with and without Type 2 diabetes were paraffin embedded. The expression of CGRP, GABA and GAD was examined in pancreatic tissue using immunofluorescence techniques., Results: CGRP, GABA and GAD were observed in many cells located in the central as well as the peripheral regions of pancreatic islet. The expression of CGRP, GABA and GAD decreased dramatically in pancreatic islet cells of diabetic patients compared to control. CGRP and GABA co-localized with glucagon in some pancreatic islet cells of both normal and diabetic patients. The pattern of distribution of CGRP, GABA and GAD in normal and Type 2 diabetic patients was similar to that of insulin., Conclusion: The number of human pancreatic islet cells expressing CGRP, GABA and GAD decreased significantly after the onset of Type 2 diabetes. These neuropeptides and neurotransmitters may play a role in the regulation of pancreatic beta cell function.

Diabetes mellitus (DM) is recognized as one of the leading causes of morbidity and mortality in the world. About 5-6% of the world population suffers from this disease and the number of people diagnosed with diabetes is rapidly increasing. Diabetes has been demonstrated to be associated with oxidative stress and hyperglycemia, one of the most important indicators of oxidative stress. The endogenous mechanisms of enzymes and antioxidants are able to destroy the reactive species and create a balance between antioxidant and free radicals. In diabetes, the oxidative stress is increased because of the deficiency in the antioxidant defense. The intake of antioxidants, such as vitamin C, may reduce the oxidative stress associated with diabetes and hence help to restore the antioxidant defense system. The aim of this article was to investigate the effect of different doses of vitamin C on the biochemical parameters of normal and streptozotocin (STZ)-induced diabetic rats. Biochemical analysis was used to study the effect of this vitamin on the biochemical parameters of normal and diabetic rats. Liver and kidney enzymes were elevated after the onset of diabetes. Moderate doses of vitamin C significantly (P < 0.0008) reduced plasma gamma-glutamyl level in diabetic rats. Moreover, vitamin C significantly (P < 0.01) reduced the blood urea nitrogen level of diabetic rats. The plasma level of electrolytes, such as calcium and sodium, also changed significantly (P < 0.00001) after oral administration of vitamin C. Antioxidants, such as vitamin C, may ameliorate the biochemical parameters of diabetic rats.

Objective: To examine the effect of ipamorelin (IPA), a novel pentapeptide with a strong growth hormone releasing potency, on insulin secretion from pancreatic tissue fragments of normal and diabetic rats., Materials and Methods: Diabetes mellitus was induced by streptozotocin (60 mg kg(-1)). Four weeks after the induction of diabetes, pancreatic tissue fragments of normal and diabetic rats were removed and incubated with different concentrations (10(-12) - 10(-6) M) of IPA. Insulin release from the pancreas was measured by radioimmunoassay., Results: Ipamorelin evoked significant (p<0.04) increases in insulin secretion from the pancreas of normal and diabetic rats. Either diltiazem or yohimbine or propranolol or a combination of atropine, propranolol and yohimbine inhibited IPA-evoked insulin secretion significantly (p<0.03) from the pancreas of normal and diabetic rats. Atropine caused a significant (p<0.007) reduction in the IPA-induced insulin secretion in diabetic but not in normal rats., Conclusion: IPA stimulates insulin release through the calcium channel and the adrenergic receptor pathways. This is the first study to examine the effect of ipamorelin on insulin secretion in the pancreas.

Xerostomia (oral dryness sensation) is due to dryness of the oral cavity and it is more prevalent in the elderly. This study investigated the effect of ageing on parotid gland structure and function of control (2-6 months) and aged (12, 16-18 and 22-24 months) rats employing light microscopic, colorimetric, gas chromatographic and microspectrofluorimetric methods to investigate the morphological changes of the parotid glands, amylase release, endogenous lipid distribution and cytosolic free calcium levels, respectively. When compared to controls, age-related changes were apparent in glands obtained from rats aged 16-18 and 22-24 months, which included reduced acinar cell distribution, enlarged parotid ducts with fatty and connective tissue and mast cell infiltrations. Parotid acini from 12, 16-18 and 22-24-month-old glands showed significant (p < 0.05) age-related decreases in amylase release, compared to controls when challenged with acetylcholine (ACh). No change in basal calcium signals was observed in parotid acini from 2-6 to 16-18-month-old-animals. However, stimulation of 16-18-month-old parotid acini with 10(-5)M ACh resulted in a significant (p < 0.001) decrease in both peak and plateau phases of the cytosolic Ca2+ signal when compared to control. Gas chromatography of de novo and essential acyl lipids revealed no changes in the amount of either acyl lipid group in glands obtained from 2-6 to 22-24-month-old animals. Lipid analysis of phospholipid associated acyl chains showed a higher relative proportion of linoleic acid in older glands. The results reveal that ageing is associated with marked and distinct morphological changes including infiltrations of lipids and mast cells of the parotid gland and decreases in amylase release and cytosolic Ca2+ signals.

Diabetes mellitus is one of the most common endocrine diseases. In UAE many traditional plants such as the Citrullus colocynthis (Handal) are used as antidiabetic remedies. The aim of this study was to examine the effect of the aqueous extract of the seed of C. colocynthis on the biochemical parameters of normal and streptozotocin (STZ)-induced diabetic rats. Diabetes mellitus was induced by a single intraperitoneal (60 mg/kg body wt1) injection of STZ. Normal and diabetic rats were fed with the plant extract daily by oral intubation for 2 weeks. Blood sample were collected at the beginning and end of the experiment for the measurement of biochemical parameters. The plasma level of alanine aminotranferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), lactic dehydrogenase (LDH) increased significantly after the onset of diabetes. Oral administration of the plant extract reduced the plasma level of AST and LDH significantly. However, the plant extract failed to reduce the increased blood level of GGT and ALP in diabetic rats. Blood urea nitrogen (BUN) increased significantly after the onset of diabetes. No significant difference was observed in the blood creatinine, K+, Na+, Ca2+ and P levels of normal and diabetic rats. The plant extract did not have any effect on BUN level, however, it caused an increase in the level of K+, Na+ in diabetic rats. In conclusion, oral administration of the aqueous extract of the C. colocynthis can ameliorate some of the toxic effects of streptozotocin.

Objective: Ghrelin is a newly discovered peptide, which was first demonstrated in the epithelium of rat stomach. The purpose of the study was to examine the effect of ghrelin on glucagon secretion from pancreatic tissue fragments of normal and diabetic rats., Methods: Diabetes was induced by streptozotocin (60 mg Kg body weight 1) given intraperitoneally. Four weeks after the onset of diabetes, pancreatic fragments of normal and diabetic rats were incubated with different concentrations (10 12 10 6 M) of ghrelin. Glucagon release was measured using radioimmunoassay technique., Results: Ghrelin failed to stimulate or inhibit glucagon secretion from normal rat pancreas. However, it induced significant increases in glucagon secretion from pancreatic tissue fragments of diabetic rats. Either atropine (muscarinic cholinergic receptor antagonist) or propranolol (beta-adrenergic receptor antagonist) or yohimbine (alpha2-adrenergic receptor antagonist) or diltiazem (calcium channel antagonist) did not affect ghrelin-glucagon interaction. Moreover, a combination of atropine, propranolol and yohimbine had no significant effect on the interaction of ghrelin with glucagon., Conclusion: The ghrelin-induced glucagon secretion in diabetic rats is not controlled via cholinergic or adrenergic pathways. In conclusion, it appears that the main target of ghrelin in the rat endocrine pancreas is not glucagon-producing cells but rather insulin secreting cells which are more involve in weight gain and body growth.

OBJECTIVES: The distribution of serotonin (5-HT) and its effect on insulin and glucagon secretion were investigated to examine whether there are changes in the pattern of distribution and effect of 5-HT after the onset of experimental diabetes. METHODS: The pattern of 5-HT and its effect of insulin and glucagon secretion was examined using immunohistochemical and radioimmunoassay techniques, respectively. RESULTS: 5-HT was demonstrated mainly in the neural elements of the pancreas. 5-HT-containing fine varicose nerve fibers were discerned in the wall of blood vessels and pancreatic ducts. 5-HT-containing nerves were also observed in the periacinar and periinsular regions of normal pancreas. The pattern or intensity of the distribution of serotonergic nerves did not change after the onset of diabetes. The perivascular, periductal, periacinar and periinsular regions of diabetic pancreas all contained 5-HT positive nerves. 5-HT elicited marked increases in insulin secretion from normal pancreas but had an inhibitory effect on insulin secretion from diabetic pancreatic tissues. In contrast, 5HT inhibited glucagon secretion from normal pancreatic tissue fragments but stimulated glucagon release from diabetic pancreatic tissue fragments. conclusion: 5-HT is well distributed in normal and diabetic pancreatic tissues and has stimulatory effects on insulin secretion from normal pancreas and glucagon secretion from diabetic pancreas. This result indicates that although 5-HT may help in the maintenance of the blood sugar level in normal pancreas by increasing insulin secretion and decreasing glucagon secretion, it may also aggravate the hyperglycemia observed in diabetes mellitus and hence exacerbate the symptoms of hyperglycemia in poorly controlled diabetes mellitus.