Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The intraportal injection of 350 to 1,000 isolated islets into streptozotocin-diabetic rats immediately normalized (approximately 24 hours) fasting plasma glucose and insulin levels. Polyuria, polydipsia, and hyperglucagonemia disappeared more gradually over a 2-to-12-week period--the time required for normalization varying with the severity of the diabetes and the number of islets transplanted. In long-term islet-transplanted rats (greater than five months), the hepatic insulin and glucagon reserves averaged 50 per cent and 25 per cent, respectively, of the corresponding normal pancreatic hormone content. Glucagon was increased slightly in the pancreas of streptozotocin-diabetic rats and decreased considerably in transplanted animals. However, total pancreatic glucagon (i.e. pancreatic and hepatic reserves) in transplanted animals was the same as the pancreatic content of normal control rats, indicating the presence of feedback control mechanism(s) in the regulation of pancreatic glucagon reserves. Long-term transplanted islets demonstrated well-granulated A-, B-, and D-cell movement out of the vascular space and the formation of narrow intercellular spaces and junctional complexes with surrounding hepatocytes.
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PMID:Metabolic and morphologic studies in intraportal-islet-transplanted rats. 13 76

We experienced a chronic alcoholic patient in whom a large intake of alcohol led to the development of frank clinical diabetes, and glucose intolerance and insulin deficiency improved perfectly following abstinence from alcohol. The patient was a 31-year-old male with no diabetes among his relatives. He was a heavy drinker since 12 years, and especially had a large intake of alcohol from Dec. 25 '84 to Jan. 3 '85. From the end of Jan. 1985 he complained of thirst, polydipsia, polyuria and body weight loss from 94 to 69 Kg. On June 25 1985 he admitted for the treatment of diabetes and had abstinence from alcohol. The blood glucose and HbA1 levels were 291 mg/dl and 14.7%, respectively on admission. His 75 g OGTT was diabetic in type and serum insulin response to glucose decreased markedly. Liver function tests were normal, and islet cell antibody was negative. Blood adrenaline, noradrenaline, growth hormone, glucagon, cortisol, T3 and T4 levels were normal. FBS, HbA1 and 75 g OGTT recovered to normal by dietary treatment (1800 kcal) with oral hypoglycemic agents for 8 weeks. This case report suggests that the cause of alcohol-induced diabetes is probably due to impairment of insulin secretion by either alcohol itself or alcohol metabolites.
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PMID:[A chronic alcoholic patient with the development of frank diabetes after heavy drinking and perfect improvement following abstinence from alcohol]. 152 26

Outbred Wistar rats were randomly assigned to three experimental groups: GI, 10 nondiabetic control rats; GII, 10 alloxan-diabetic control rats; GIII, 25 alloxan-diabetic rats that received pancreaticoduodenal transplantation (PDT) from normal donor Wistar rats and were immunosuppressed with cyclosporin A. For 7 prior and 4, 7, 14, 21, and 30 days posttransplantation (during which the animals were housed in metabolic cages for periods of 24 hours) body weight, water and food intake, urine output, blood and urinary glucose, plasma insulin, and glucagon were recorded. These parameters were also concurrently recorded for diabetic and nondiabetic control rats. Animals were sacrificed after 30 days and histological and immunohistochemical studies of the pancreas were performed. Pancreatic transplants consistently and significantly improved the metabolic abnormalities of the diabetic rat (P less than 0.01) by restoring body weight gain, and by immediate relief of hyperglycemia, glucosuria, polyuria, polydipsia, and also the low levels of plasma insulin. The plasma glucagon, elevated in diabetic control rats, did not change after transplant.
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PMID:Metabolic effect of pancreaticoduodenal transplantation in diabetic rats. 159 82

A case of pituitary dependent hyperadrenocorticism in a horse is reported. Clinical signs included hirsutism, polydipsia and general debility. The horse was persistently hyperglycaemic and glucose values were unchanged following subcutaneous administration of insulin. Resting cortisol values were normal, but dexamethasone suppression of cortisol concentration was shorter than normal. Plasma glucose, cortisol, insulin and glucagon concentrations were measured as part of an intravenous glucose tolerance test. The patient responses were different from those in a control pony.
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PMID:Glucose metabolism in a pony mare with a tumour of the pituitary gland pars intermedia. 333 Jun 56

The mechanisms by which the beta cells of pancreatic islets are destroyed in insulin-dependent diabetes mellitus (IDDM) are poorly understood. In this report the pancreatic histo- and immunopathology of two children, both HLA-DR 3/4, DQ 2/8 positive and who both died from cerebral oedema within a day of clinical diagnosis of IDDM, were investigated. Patient 1, a 14-month-old girl, had a 4-week history of polydipsia and polyuria. Patient 2, a 3-year-old boy, had 2 days of illness. Both patients had a similarly severe loss of insulin cells but differed markedly as to the extent of lymphocytic islet infiltration (insulitis). Apart from insulitis, marked islet macrophage infiltration was demonstrated in both patients with the HAM-56 monoclonal antibody. Neither patient showed aberrant expression of HLA class II antigens on insulin-immunoreactive cells, but allele-specific HLA-DQ8 expression was evident on endothelial cells. Glutamic acid decarboxylase immunoreactivity was detected in both insulin- and glucagon-immunoreactive cells. It is concluded that the heterogeneity of islet pathology, especially insulitis, may reflect different dynamics and extent rather than different pathomechanisms of immune destruction of islets in IDDM.
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PMID:Heterogeneity of islet pathology in two infants with recent onset diabetes mellitus. 769 19

The diabetogenic effects of streptozotocin (STZ) were studied on blood glucose, plasma insulin, feeding and drinking, body weight, islet morphology, and hypothalamic serotonin (5-HT) release in vehicle-pretreated rats and in rats pretreated with either intracerebroventricular injection of 5,7-dihydroxytryptamine (5,7-DHT; a 5-HT nerve fiber depletor), intraperitoneal injection of p-chlorophenylalanine (PCPA; a tryptophan hydroxylase inhibitor), or intraperitoneal injection of p-chloroamphetamine (PCA; a neurotoxin for 5-HT nerve fiber). At four days after STZ administration, vehicle-treated rats displayed hyperglycemia, polydipsia, polyphagia, decreased plasma insulin level, derangement of islet morphology (few insulin cells, accumulation of glucagon cells), and elevated 5-HT release in the hypothalamus. The above diabetogenic effects of STZ were attenuated by brain serotonin depletion induced by 5,7-DHT, PCPA, or PCA. Furthermore, the STZ-induced hyperglycemia or derangement of islet morphology was attenuated by peripheral sympathectomy or adrenalectomy. It is concluded that brain serotonin depletion attenuates diabetogenic effects of STZ by reducing sympathetic efferent activity in rats.
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PMID:Brain serotonin depletion attenuates diabetogenic effects of streptozotocin. 776 35

Two weeks after intraportal transplantation of 2,000 neonatal pancreatic islets, recipient rats completely recovered from streptozotocin-induced diabetes. The reversal of diabetes could be documented by the normalization of blood glucose levels, by a restored weight gain, by normal glucagon and insulin levels in blood, and by a disappearance of polyuria and polydipsia. The reversal remained stable for at least 9 months. This study determined whether intraportally transplanted pancreatic islets were reinnervated after transplantation and whether the secretion of insulin and glucagon from pancreatic islets might be modulated by the vegetative innervation of recipient livers. Predominantly catecholaminergic but also cholinergic nerve fibers were detected not only within the portal tracts around hepatic arteries, portal veins, and bile ducts, but also at the borderline of hepatocytes and beta-cells and in islet cell complexes between beta-cells. Corresponding electron micrographs showed beta-cells in close contact with axons of nonmyelinated nerve fibers. Isolated livers were single pass perfused via both the hepatic artery and the portal vein. An increase in glucose level from 5 to 14 mmol/l enhanced hepatic glucose uptake and increased insulin secretion from transplanted islets with a biphasic secretion profile but had no effect on glucagon output. Stimulation of the nerve plexus around the hepatic artery and the portal vein (7.5 Hz, 2 min), which activates primarily the sympathetic system, not only reduced glucose uptake and perfusion flow but also completely reversed the glucose-stimulated increase in insulin secretion. Nerve stimulation did not influence glucagon secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intraportal transplantation of pancreatic islets into livers of diabetic rats. Reinnervation of islets and regulation of insulin secretion by the hepatic sympathetic nerves. 792 10

Pathomorphologic studies were carried out on three cases of bovine diabetes mellitus with clinical signs of polydipsia, polyuria, severe emaciation, glycosuria, persistent hyperglycemia, and decreased glucose tolerance. At necropsy, two animals had atrophy of the pancreas, whereas other visceral organs, including the endocrine organs, showed no significant changes. Microscopically, there was atrophy and reduced numbers of pancreatic islets accompanied by interlobular and interacinar fibrosis and compensatory enlargement of some remaining islets. Lymphocytes were observed commonly around and within atrophic islets and occasionally around and within enlarged islets. Vacuolar degeneration with occasional accumulation of glycogen granules was observed in the beta-cells of these enlarged islets. Immunohistochemical studies of atrophic islets demonstrated complete loss of beta-cells or only a few small beta-cells. There also was a corresponding decrease in the number of cells that stained with anti-glucagon (alpha-cells) or anti-somatostatin (delta-cells) antibodies. The vacuolated cells in the enlarged islets stained strongly with anti-insulin antibody (beta-cells). Ultrastructurally, the majority of cells in the atrophic islets had reduced cytoplasmic volume and few secretory granules, features consistent with alpha-cells. In contrast, enlarged islets that had prominent immunohistochemical staining for insulin (beta-cells) consisted of beta-cells with cytosolic edema, mitochondrial swelling, dilated smooth endoplasmic reticulum, and reduced numbers of or degranulated secretory granules. These pathomorphologic features found in cattle are similar to those found in juvenile-onset insulin-dependent diabetes mellitus in human beings and suggest autoimmune involvement in diabetes.
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PMID:Spontaneous diabetes mellitus in young cattle: histologic, immunohistochemical, and electron microscopic studies of the islets of Langerhans. 844 27

Tumor-associated hypoglycemia has been reported in dogs with pancreatic beta-cell tumors, hepatic tumors, and, rarely, with other neoplasms. This article describes 4 dogs with marked hypoglycemia associated with smooth muscle tumors (jejunal leiomyoma, gastric leiomyoma and leiomyosarcoma, and splenic leiomyosarcoma). Presenting clinical signs included grand mal seizures, lethargy, weakness, ataxia, and, in 1 dog, polyuria/polydipsia. The serum insulin concentration was low in 1 dog and normal in the other dog evaluated. Immunohistochemical staining for insulin was negative in the 4 tumors; the 3 tumors arising from the stomach and jejunum stained diffusely positive for glucagon. Blood glucose concentrations rapidly returned to normal after complete surgical resection of the tumors, and clinical signs associated with hypoglycemia resolved. Long-term follow-up available in 3 of the 4 dogs found no recurrence of clinical signs related to hypoglycemia at 15, 31, and 38 months after surgery, respectively.
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PMID:Hypoglycemia in four dogs with smooth muscle tumors. 855 89

Medical records of 10 cats with transient clinical diabetes mellitus were reviewed. At the time diabetes was diagnosed, clinical signs included polyuria and polydipsia (10 cats), weight loss (8 cats), polyphagia (3 cats), lethargy (2 cats), and inappetence (1 cat). Mean (+/- SD) fasting blood glucose concentration was 454 +/- 121 mg/dL, mean blood glucose concentration during an 8-hour period (MBG/8 hours) was 378 +/- 72 mg/dL, and glycosuria and trace ketonuria were identified in 10 and 5 cats, respectively. Baseline serum insulin concentration was undetectable (6 cats) or within the reference range (4 cats) and serum insulin concentration did not increase after i.v. glucagon administration in any cat. Insulin-antagonistic drugs were being administered to 5 cats and concurrent disorders were identified in all cats. Management of diabetes included administration of glipizide (6 cats), insulin (3 cats), or both (1 cat), discontinuation of insulin-antagonistic drugs, and treatment of concurrent disorders. Insulin and glipizide treatment was discontinued 4-16 weeks (mean, 7 weeks) after the initial diagnosis of diabetes was confirmed. At the time treatment for diabetes was discontinued, clinical signs had resolved, mean fasting blood glucose concentration was 102 +/- 48 mg/dL, MBG/ 8 hours was 96 +/- 32 mg/dL, glycosuria and ketonuria were not identified in any cat, and concurrent disorders (except mild renal insufficiency in 1 cat) had resolved. Significant (P < .05) increases occurred in postglucagon serum insulin concentrations, insulin peak response, and total insulin secretion, compared with values obtained when clinical diabetes was diagnosed. Histologic abnormalities were identified in pancreatic islets of 5 cats in which pancreatic biopsies were obtained and included decreased number of islets (4 cats), islet amyloidosis (3 cats), and vacuolar degeneration of islet cells (3 cats). Mean beta cell density was significantly (P < .001) decreased in diabetic cats compared with control cats (1.4 +/- 0.7 versus 2.6 +/- 0.5%, respectively). Cells within islets stained positive for insulin, however, the number of insulin-staining cells per islet and the intensity of insulin staining were decreased in 5 and 2 cats, respectively. Clinical diabetes had not recurred in 1 cat after 6 years, in 4 cats lost to follow-up after 1.5, 1.5, 2.0, and 2.5 years, and in 2 cats that died 6 months and 5.5 years after clinical diabetes resolved. Clinical diabetes recurred in 3 cats after 6 months, 14 months, and 3.4 years, respectively. These findings suggest that cats with transient clinical diabetes have pancreatic islet pathology, including decreased beta cell density, and that treatment of diabetes and concurrent disorders results in improved beta cell function, reestablishment of euglycemia, and a transition from a clinical to subclinical diabetic state.
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PMID:Transient clinical diabetes mellitus in cats: 10 cases (1989-1991). 1005 60


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