Changes Of Pancreatic Beta-cells Research Articles

Comparative effects of curcumin versus nano-curcumin on histological, immunohistochemical expression, histomorphometric, and biochemical changes to pancreatic beta cells and lipid profile of streptozocin induced diabetes in male Sprague–Dawley rats

Diabetes mellitus is a worldwide problem characterized by hyperglycemia as well as the damage of the microscopic structure of the beta cells of Langerhans pancreatic islets. In the present study, the histological, immunohistochemical, morphometric, and biochemical alterations to pancreatic beta cells in streptozocin (STZ)-induced diabetes were assessed in rats treated with curcumin (CU) (100 mg/kg/day) or nano-curcumin (nCU) (100 mg/kg/day) for 1 month. Twenty-four adult male Wistar albino rats were distributed into four groups: the nondiabetic control group, the diabetic untreated group, and two diabetic groups treated with CU or nCUR, respectively. Blood glucose, serum insulin levels, and lipid profile were measured. The pancreatic tissues were collected and processed into paraffin sections for histological and immunohistochemical examination, oxidative stress markers, and real-time PCR expression for pancreatic and duodenal homeobox 1 (PDX1). The insulin expression in beta cells was assessed using immunohistochemistry. Morphometrically, the percentage area of anti-insulin antibody reaction and the percentage area of islet cells were determined. STZ-induced deteriorating alteration in beta cells led to declines in the number of functioning beta cells and insulin immunoreactivity. In STZ-treated rats, CU and nCUR significantly reduced blood glucose concentration while increasing blood insulin level. It also caused a significant increase in the number of immunoreactive beta cells to the insulin expression and significant reduction of the immunoreactive beta cells to the caspase-3 expression. In conclusion, CU and nCUR could have a therapeutic role in the biochemical and microscopic changes in pancreatic beta cells in diabetes-induced rats through STZ administration with more bio-efficacy of nCUR.

Epigenetic Changes Induced by High Glucose in Human Pancreatic Beta Cells.

Epigenetic changes in pancreatic beta cells caused by sustained high blood glucose levels, as seen in prediabetic conditions, may contribute to the etiology of diabetes. To delineate a direct cause and effect relationship between high glucose and epigenetic changes, we cultured human pancreatic beta cells derived from induced pluripotent stem cells and treated them with either high or low glucose, for 14 days. We then used the Arraystar 4x180K HG19 RefSeq Promoter Array to perform whole-genome DNA methylation analysis. A total of 478 gene promoters, out of a total of 23,148 present on the array (2.06%), showed substantial differences in methylation (p < 0.01). Out of these, 285 were hypomethylated, and 193 were hypermethylated in experimental vs. control. Ingenuity Pathway Analysis revealed that the main pathways and networks that were differentially methylated include those involved in many systems, including those related to development, cellular growth, and proliferation. Genes implicated in the etiology of diabetes, including networks involving glucose metabolism, insulin secretion and regulation, and cell cycle regulation, were notably altered. Influence of upstream regulators such as MRTFA, AREG, and NOTCH3 was predicted based on the altered methylation of their downstream targets. The study validated that high glucose levels can directly cause many epigenetic changes in pancreatic beta cells, suggesting that this indeed may be a mechanism involved in the etiology of diabetes.

Molecular Mechanisms of Hawthorn Extracts in Multiple Organs Disorders in Underlying of Diabetes: A Review.

Diabetes mellitus (DM) is one of the most important metabolic disorders associated with chronic hyperglycemia and occurs when the body cannot manage insulin secretion, insulin action, or both. Autoimmune destruction of pancreatic beta cells and insulin resistance are the major pathophysiological factors of types 1 and 2 of DM, respectively. Prolonged hyperglycemia leads to multiple organs dysfunctions, including nephropathy, neuropathy, cardiomyopathy, gastropathy, and micro- and macrovascular disorders. The basis of the metabolic abnormalities in carbohydrate, fat, and protein in diabetes is insufficient action of insulin on various target tissues. Medicinal plants are rich sources of bioactive chemical compounds with therapeutic effects. The beneficial effects of leaves, fruits, and flowers extracts of Crataegus oxyacantha, commonly called hawthorn, belonging to the Rosaceae family, are widely used as hawthorn-derived medicines. Data in this review have been collected from the scientific articles published in databases such as Science Direct, Scopus, PubMed, Web of Science, and Scientific Information Database from 2000 to 2021. Based on this review, hawthorn extracts appear both therapeutic and protective effects against diabetic-related complications in various organs through molecular mechanisms, such as decreasing triglyceride, cholesterol, very low density lipoprotein and increasing the antioxidant activity of superoxide dismutase, catalase, glutathione peroxidase, total antioxidant capacity, decreasing malondialdehyde level, and attenuating tumor necrosis factor alpha, interleukin 6 and sirtuin 1/AMP-activated protein kinase (AMPK)/nuclear factor kappa B (NF-κB) pathway and increasing the phosphorylation of glucose transporter 4, insulin receptor substrate 1, AKT and phosphoinositide 3-kinases, and attenuating blood sugar and regulation of insulin secretion, insulin resistance, and improvement of histopathological changes in pancreatic beta cells. Collectively, hawthorn can be considered as one new target for the research and development of innovative drugs for the prevention or treatment of DM and related problems.

An immunohistochemical and biochemical evidences of pancreatic β-cell regeneration in type 2 diabetic rats after treated with Aegle marmelos leaf extract and Aegeline

The study aims to investigate the Immunohistochemical changes in pancreatic beta cells in fructose fed, streptozocin (STZ) induced Type 2 Diabetes (T2DM) rats treated with various doses of leaf extract of Aegle marmelos (AAM) and Aegeline (AG). 42 adult male wistar albino rats were separated into 7 groups, including Vehicle Control (VC); T2DM; T2DM + AAM 250 mg/kg; T2DM + AAM 500 mg/kg; T2DM + AG 20mg/kg; T2DM + AG 50 mg/kg and T2DM + AG 100 mg/kg. Experimental T2DM was created by a single dose of 40 mg/kg STZ injection intra-peritoneally along with 10% of fructose solution given orally for 30 days. Calculated dosages of AAM and AG were given with oral gavage for 30 days. Pancreas was harvested and processed. Slides were stained using hematoxylin and eosin (H&amp;E) stains. Insulin expressing beta-cells was analyzed using immunohistochemistry. Fructose fed, STZ induced rats showed degenerative expressions in beta-cells. In STZ treated rats, AG reduced the blood glucose concentration and serum insulin levels at the maximum functional dose compared to AAM. The immunohistochemical information suggests that the AG at 100 mg/kg dose has the capability of making the dormant cells to reproduce to restore the lost cells of islets of Langerhans.

Epigenetic regulation of insulin: role of glucose in pancreatic beta cells.

Type 2 diabetes mellitus (T2DM) is a metabolic disease which is associated with both insulin secretory dysfunction and insulin resistance. Glucose appears to play a pivotal role in the regulation of insulin synthesis and secretion, the mechanism known as glucose-stimulated insulin secretion (GSIS). Glucose plays a major role in the expression of insulin gene via the recruitment of transcription factors to the insulin gene and the regulation of its histone modifications, resulting in insulin secretion. Conversely, chronic hyperglycaemia induces the dysfunction of pancreatic beta cells and insulin resistance. Hence, the role of epigenetics in the physiological role of glucose in insulin secretion and chronic hyperglycemia, and subsequent T2DM have been explored. A better understanding of the epigenetics is crucial to explore new strategies to treat the disease. This review highlights the role of epigenetics during the physiological and pathological changes in pancreatic beta cells to improve the understanding of how these changes contribute to the development of T2DM.

The Role of Epigenetic Changes in Pancreatic Beta Cells in Diabetes

IntroductionDiabetes mellitus is a condition in which either the pancreas does not produce enough insulin, or the cells of the body do not respond properly to the insulin produced, resulting in high levels of sugar in the bloodstream. We hypothesized that epigenetic changes in pancreatic beta cells in the pancreas, the main insulin‐producing cells in the body, may contribute to the etiology of diabetes.MethodsTo test this hypothesis, we treated human pancreatic beta cells derived from induced pluripotent stem cells (iPSCs) with either high (20 mM) or low (2 mM) glucose for 14 days.ResultsWe found epigenetic changes in several hundred genes, including those involved in many signaling pathways, especially glucose metabolism and insulin secretion. Other pathways affected were those involved in oxytocin metabolism, gastric acid secretion, calcium signaling, and adrenergic signaling.ConclusionOur study suggests that diabetes may, at least in part, be caused by epigenetic changes in pancreatic beta cells. image imageThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Glucocorticoid-Induced, Morpho-Functional Alterations in Pancreatic Beta Cells of Wistar Rats

Background: Though prolonged use of glucocorticoids has been reported to promote adverse effects, traditionally, high-dose glucocorticoids have been implicated in immune-suppression following organ transplant with Cortisone being a well-known artificial glucocorticoid.&#x0D; Objectives: This study investigated the histo-architectural and functional changes in pancreatic beta cells due to Cortisone administration.&#x0D; Materials and Methods: Forty two (42) Wistar rats (140 – 200 kg) were assigned into seven groups of six (6) rats each with group A acting as a control. While groups B and C were respectively treated with 0.1 mg/kg and 0.3 mg/kg of Cortisone, groups D and E received 0.1 mg/kg and 0.3 mg/kg of Cortisone respectively plus 33 mg/kg of Ketoconazole; whereas, groups F and G were respectively given 0.1 mg/kg and 0.3 mg/kg of Cortisone alongside 150 mg/kg of Vitamin E each for twenty-eight (28) days. After 28 days of administration, rats were euthanized and blood samples collected for insulin assay. Pancreatic tissues were also harvested and observed for histo-morphological changes.&#x0D; Results: Analysis of variance (ANOVA) found Cortisone to have significantly (p &lt; .05) increased glucose level in a dose dependent manner. This was however attenuated following co-administration of Ketoconazole and Vitamin E as Ketoconazole showed more potency in this ameliorating effect. Also, Cortisone was observed to significantly decrease (in dose dependent fashion), pancreatic β-cell functions, with attenuating effect seen following co-administration of Ketoconazole.&#x0D; Conclusion: It is recommended that caution is applied with the intake of glucocorticoids, especially in polypharmacy while treating certain ailments.

A histological and immunohistochemical study of beta cells in streptozotocin diabetic rats treated with caffeine.

In this study, the histological, immunohistochemical, morphometric, and biochemical changes to pancreatic beta-cells in STZ-induced diabetes were evaluated in rats treated with different doses of caffeine. Fifty adult male Wistar albino rats were divided into five groups: the nondiabetic control group, the diabetic untreated group, and three diabetic groups treated with different doses of caffeine (10, 50, and 100 mg/kg/day). Blood glucose and serum insulin levels were measured. The pancreata were collected and processed into paraffin sections. They were stained using hematoxylin and eosin (H&E) and Masson trichrome stains. The insulin expression in beta-cells was assessed using immunohistochemistry. Morphometrically, the percentage area of anti-insulin antibody reaction, the percentage of beta-cells per total islet cell number, and the average area of the islets were determined. STZ-induced degenerative changes in beta-cells led to decreases in the number of functioning beta-cells and insulin immunoreactivity and to increases in the number of collagen fibers in the islets. In STZ-treated rats, caffeine significantly decreased blood glucose concentration while increasing blood insulin levels at the highest applied dose. It also induced a significant increase in the number of immunoreactive beta-cells. In conclusion, caffeine may have a protective role in the biochemical and microscopic changes in pancreatic beta-cells in diabetes induced in rats through STZ administration.

Evaluation of Antidiabetic and Antioxidant Effects of Seabuckthorn (Hippophae rhamnoides L.) in Streptozotocin-Nicotinamide Induced Diabetic Rats

Seabuckthorn (Hippophae rhamnoides L.) is a branched deciduous shrub native to Europe and Asia. The plant has been used extensively in oriental traditional system of medicine for treatment of different diseases. Seabuckthorn is found to have significant antioxidative, antimicrobial, immunomodulatory, cytoprotective, hepatoprtective and tissue regenerative properties. The present study was undertaken to evaluate the antidiabetic and antioxidant effect of seabuckthorn (Hippophae rhamnoides L.) in streptozotocin-nicotinamide induced type-2 diabetic rats. Experimental diabetes was induced by a single intraperitonial injection of streptozotocin (60 mg/kg), 15 minutes after the i.p. administration of 120mg/kg nicotinamide. Seabuckthorn was administered orally to streptozotocin (STZ) diabetic rats. Blood glucose, tissue glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) in pancreas were estimated following the established procedures. Biochemical observations were supplemented with histological examination of pancreatic tissue. The increase of blood glucose, TBARS level with reduction in GSH content were the salient features observed in STZ- diabetic rats. Sea buckthorn produced a significant (p< 0.05) reduction in blood glucose levels and TBARS levels in the STZ- diabetic rats. GSH, reduced significantly (p< 0.05) in diabetic rats, was brought back to near normal levels by co-administration of sea buckthorn. Degenerative changes of pancreatic beta cells in STZ- diabetic rats were minimized to near normal morphology by administration of sea buckthorn as evident by histopathological examination. The results of the study indicate the role of oxidative stress in the induction of diabetes and suggest a protective effect of sea buckthorn in this animal model.

N-acetylcysteine an Allium plant compound protects against chromium (VI) induced oxidant stress and ultrastructural changes of pancreatic beta-cells in rats

The present study was carried out to determine the effectiveness of N-acetylcysteine (NAC) in alleviating chromium (VI)-induced beta-cell damages in rats. Sixty male albino rats were randomly divided into four groups (n = 15/group). Group I remained untreated; Group II received single dose of potassium dichromate (50 mg/kg b.w., s.c.); Group III received NAC (200 mg/kg b.w., i.p.) before chromium (VI) injection (50 mg/kg b.w., s.c.); Group IV received NAC alone (200 mg/kg b.w., i.p.). Pancreatic tissue malondialdehyde (a marker of lipid peroxidation), pancreas antioxidant power, blood glucose level and ultrastructure of beta-cells were evaluated. Results showed that the administration of chromium (VI) resulted in a state of pancreatic injury and extensive oxidative damage in rats as manifested by the increase in lipid peroxidation and the decrease in activities of antioxidant enzymes such as glutathione peroxidase and catalase. In serum, there was significant increase in the level of glucose in these animals. Administration of NAC shortly prior to chromium (VI) significantly mitigated most of these changes to control values. Based on ultrastructural observations, the administration of NAC may effectively rescue beta-cells from oxidative damage without affecting their function and structural integrity. It can be concluded that NAC if administrated before chromium (VI) injection improves glycemic state by enhancing insulin secretion and antioxidant competence in pancreatic beta-cells.

Ultrastructural and functional changes of pancreatic beta-cells in rats with MODS

Objective To explore the effect of multiple organ dysfunction syndrome (MODS) on the ultra-structure and function of pancreatic beta cells and to provide a theoretical basis for clinical treatment of high blood glucose in patients with MODS. Method This study was performed in the Animal Department of Fujian Provincial Hospital, the Key Laboratory of Fujian Provincial Cardiovascular Institute, the Pathology Department of Fujian Provincial Hospital and in the Electron Microscopic Department of Fujian Medical University. Sixteen pathogen-free male Sprague-Dawley rots weighing 180 ～ 220 g, were selected and randomly divided into MODS group and control group (8 rats per group). MODS was induced by intraperitoneal injection with bacterium c oli and cutting the left legs. Rats in the control group received an intraperitoneal injection of an equivalent volume of sodium chloride. The MODS model was considered successful when two or more organs showed dysfunction 48 h after the injection. The blood glucose and plasma insulin levels were measured in the fasting state and in response to a glucose load. All data were analyzed using t tests. The plasma insulin concentration was analyzed after logarithmic transforma-tion. The ultrastructure of the pancreatic beta cells was observed under an electron microscope. The expression of Bax was determined immunohistochemically. Results The blood glucose during fasting, the blood glucose level 30 min after a glucose load and the expression of Bax were significantly in the MODS group compared with the con-trol group (P <0.01). In addition, the plasma insulin concentration level was insignificantly increased 30 min af-ter the glucose load in the MODS group (P < 0.01). Pathological uhrastructural changes were found, as follows: most pancreatic beta cells in the MODS group exhibited vacuole degeneration, some were necrotized, the mitochen-dria had swollen and the rough endoplasmic reticulum had expanded. Conclusions The uhltrastructure of the pan-creatic beta cells in the MODS rats shewed significant pathologic changes, with increased expression of Bax. These pathological changes may he responsible for the decreased insulin secretion, which caused the increased blood glu-cose levels. Key words: MODS; Pancreatic beta cells; Ultrastmcture; Pathologic changes; Insulin; Blood glucose; Bax; Rat

Protective effects of the volatile oil of Nigella sativa seeds on β-cell damage in streptozotocin-induced diabetic rats: a light and electron microscopic study

The aim of this study was to evaluate the possible protective effects of the volatile oil of Nigella sativa (NS) seeds on insulin immunoreactivity and ultrastructural changes of pancreatic beta-cells in STZ-induced diabetic rats. STZ was injected intraperitoneally at a single dose of 50 mg/kg to induce diabetes. The rats in NS treated groups were given NS (0.2 ml/kg) once a day orally for 4 weeks starting 3 days prior to STZ injection. To date, no ultrastructural changes of pancreatic beta-cells in STZ induced diabetic rats by NS treatment have been reported. Islet cell degeneration and weak insulin immunohistochemical staining was observed in rats with STZ-induced diabetes. Increased intensity of staining for insulin, and preservation of beta-cell numbers were apparent in the NS-treated diabetic rats. The protective effect of NS on STZ-diabetic rats was evident by a moderate increase in the lowered secretory vesicles with granules and also slight destruction with loss of cristae within the mitochondria of beta-cell when compared to control rats. These findings suggest that NS treatment exerts a therapeutic protective effect in diabetes by decreasing morphological changes and preserving pancreatic beta-cell integrity. Consequently, NS may be clinically useful for protecting beta-cells against oxidative stress.

Enhancement of Glucose Toxicity by Hyperbaric Oxygen Exposure in Diabetic Rats

The side effects of hyperbaric oxygen (HBO) treatment, such as oxidative stress and oxygen toxicity, have long been of interest. However, there are no comprehensive studies evaluating such toxic effects in diabetes mellitus (DM). The purpose of this study was to determine the effects of HBO on glucose homeostasis and histological changes in pancreatic beta-cells of experimentally induced diabetic rats. A total of 24 male Wistar rats were randomly divided into 4 groups: 1) Control group, no diabetic induction without HBO treatment; 2) HBO group, exposed to 100% oxygen at 2.8 ATA (atmosphere absolute) for 2 h once daily, for 7 days; 3) DM group, diabetes induced by streptozotocin (STZ) injection; and 4) DM + HBO group, received both STZ injection and HBO exposure. HBO treatment, with clinically recommended pressures and duration of therapy, was started on day 5 after STZ injection, when the blood glucose levels were significantly increased. After the last HBO treatment, the pancreatic tissues were immunostained to measure the areas of insulin immunoreactive beta-cells in the islets of Langerhans. The blood glucose increased significantly following exposure to HBO, with the highest levels achieved in rats, which had been treated with both HBO and diabetic induction. The area populated with insulin immunoreactive beta-cells decreased significantly following diabetic induction and/or HBO exposure, with the smallest area in DM + HBO group. Thus, HBO exposure enhanced the cytotoxic effect of STZ in the beta-cells of the pancreas. HBO should be cautiously employed in diabetic patients.

H2S, Endoplasmic Reticulum Stress, and Apoptosis of Insulin-secreting Beta Cells

Cystathionine gamma-lyase (CSE) is a key enzyme in the trans-sulfuration pathway, which uses L-cysteine to produce hydrogen sulfide (H2S). Functional changes of pancreatic beta cells induced by endogenous H2S have been reported, but the effect of the CSE/H2S system on pancreatic beta cell survival has not been known. In this study, we demonstrate that H2Sat physiologically relevant concentrations induced apoptosis of INS-1E cells, an insulin-secreting beta cell line. Transfection of INS-1E cells with a recombinant defective adenovirus containing the CSE gene (Ad-CSE) resulted in a significant increase in CSE expression and H2S production. Ad-CSE transfection also stimulated apoptosis. The other two end products of CSE-catalyzed enzymatic reaction, ammonium and pyruvate, had no effects on INS-1E cell apoptosis, indicating that overexpression of CSE may stimulate INS-1E cell apoptosis via increased endogenous production of H2S. Both exogenous H2S (100 microM) and Ad-CSE transfection inhibited ERK1/2 but activated p38 MAPK. Interestingly, BiP and CHOP, two indicators of endoplasmic reticulum (ER) stress, were up-regulated in H2S-and CSE-mediated apoptosis in INS-1E cells. After suppressing CHOP mRNA expression, H2S-induced apoptosis of INS-1E cells was significantly decreased. Inhibition of p38 MAPK, but not of ERK1/2, inhibited the expression of BiP and CHOP and decreased H2S-stimulated apoptosis, suggesting that p38 MAPK activation functions upstream of ER stress to initiate H2S-induced apoptosis. It is concluded that H2S induces apoptosis of insulin-secreting beta cells by enhancing ER stress via p38 MAPK activation. Our findings may help unmask a novel role of CSE/H2S system in regulating pancreatic functions under physiological condition and in diabetes.

Effects of APS on the Pathological Changes of Pancreatic beta Cells of STZ‐induced T2DM Rats

Effects of APS on the Pathological Changes of Pancreatic beta Cells of STZ‐induced T2DM Rats

Effects of Amanita phalloides toxins on insulin release: in vivo and in vitro studies

The clinical picture of Amanita phalloides poisoning includes hypoglycaemia, usually related to hepatic damage. In fact, Amanita toxins induce hepatic glycogen depletion in humans and animals. However, in animals morphological changes of pancreatic beta cells are reported, suggesting that an alteration of insulin secretion might be involved in the pathogenesis of hypoglycaemia. Therefore, we determined fasting glucose, insulin and C-peptide levels in ten patients intoxicated by Amanita phalloides and in ten control subjects. Fasting blood samples were drawn on 3 consecutive days, beginning 48-72 h after mushroom ingestion, and glucose, insulin and C-peptide concentrations were determined by routine methods. Serum glucose concentrations did not differ between poisoned subjects and controls, whereas insulin and C-peptide concentrations were significantly higher in poisoned subjects ( P<0.01), with a significant positive correlation ( R=0.97, P<0.001). We also evaluated the effects of alpha-amanitin, the main amatoxin, on in vitro insulin release. Rat islets were incubated with 5 and 50 mg/l alpha-amanitin, in the presence or absence of 5.6 mM glucose. In another protocol, islets were preincubated for 2 h with 5 and 50 mg/l alpha-amanitin in medium containing 5.6 mM glucose. After lavage, islets were incubated with increasing glucose (2.8-22.0 mM) to evaluate insulin release. In vitro, both concentrations of toxin induced insulin release (5 mg/l P<0.02, 50 mg/l P<0.01 vs controls), in the presence of 5.6 mM glucose. Islets preincubated with 5 mg/l alpha-amanitin showed a pattern of glucose-stimulated insulin release similar to controls, whereas islets preincubated with 50 mg/l alpha-amanitin showed an increased basal release with a reduced response to glucose stimulation. These observations show that Amanita toxins might play a role in the clinical context of Amanita poisoning. We demonstrate, for the first time, that alpha-amanitin induces insulin release and may exert a cytotoxic effect on beta cells.

Effect of taurine and beta-alanine on morphological changes of pancreas in streptozotocin-induced rats.

In order to determine the effects of taurine supplementation or depletion on the morphological changes of pancreatic beta-cells in streptozotocin-induced diabetic rats, Sprague-Dawley male rats were fed the purified diets supplemented with 1, 2 or 3% taurine or 5% beta-alanine in their drinking water for 7 weeks. After 3 weeks, diabetes was induced by streptozotocin injection (50 mg/kg body-weight). Pancreatic morphology was observed by transmission electron microscopy. The pancreatic beta-cell of the non-diabetic (CO) group had the many secretory granules, rough endoplasmic reticulum and rod shaped mitochondria. However, the beta-cells of non taurine-supplemented diabetic (EO) group were severely damaged, showing depleted secretory granules. In the 1% taurine-supplemented diabetic group, the beta-cells were less damaged compared to the EO group and had some apparently normal secretory granules, but most of rough endoplasmic reticulum and mitochondria was destroyed. The beta-cell of 2% taurine-supplemented diabetic group had swollen rough endoplasmic reticulum, round-shaped mitochondria and some apparently normal secretory granules. The beta-cell of 3% taurine-supplemented diabetic group was little different from that of non-diabetic group. The pancreatic beta-cell of taurine-depleted diabetic group was not destroyed but had many small secretory granules which appeared immature. This was reflected in the blood glucose concentrations of this group. Therefore, taurine may prevent insulin-dependent diabetes by protection of the pancreatic beta-cell and may also preserve normal secretory granules. From these results, taurine supplementation may be recommended for prevention and treatment of diabetes.

Ultrastructural changes in pancreatic beta cells treated with NGF and dbcAMP.

Nerve growth factor (NGF) induces morphological and physiological changes in cultured pancreatic beta-cells, including the extension of neurite-like processes. This latter effect is potentiated by dibutyryl cAMP (dbcAMP). beta-cells cultured under these conditions maintain their immunoreactivity to insulin and gamma-amino-butyric acid (GABA). NGF, dbcAMP, and high glucose concentrations also increase the expression of the GABA-synthesizing enzyme glutamic acid decarboxylase-65 in cultured beta-cells. The aim of this work was to study the effect of NGF alone or in combination with dbcAMP on pancreatic beta-cell ultrastructural morphology, after 10 days in culture. We used light microscopy, scanning electron microscopy, and transmission electron microscopy to analyze the modifications in cell surface and neurite-like projections. Morphometric analysis showed that NGF and/or dbcAMP treatment substantially increased the insulin and GABA content in granules and rough endoplasmic reticulum. Given that pancreatic beta-cells express NGF receptors and that NGF is synthesized and secreted by beta-cells, these results further suggest that NGF could have trophic actions on pancreatic hormone synthesis and/or storage.

Role of the pituitary in cyproheptadine-induced pancreatic beta-cell toxicity.

Hypophysectomized rats given cyproheptadine (40 mg/kg) for 10 days exhibited a loss of pancreatic immunoreactive insulin and ultrastructural changes in the cytoplasm of beta-cells. Sham-operated animals given cyproheptadine showed identical changes in pancreatic beta-cells except that cytoplasmic involvement progressed to the formation of large vacuoles. The pituitary is not directly involved with the cyproheptadine-induced depletion of pancreatic insulin but plays a role in the formation of large cytoplasmic vacuoles.