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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine whether synthetic somatostatin originally isolated from sheep hypothalamus can inhibit hormone secretion in the same species, we measured plasma levels of GH, insulin, glucagon, and glucose of normal sheep under a variety of experimental conditions in the presence and absence of somatostatin infusion. An oral dose of 2.5 mg./kg. 3,5-dimethypyrazole increase plasma GH from 10.9 to 376.9 ng. per milliliter, which was suppressed by 50 per cent and 80 per cent with 0.5 and 1 mg. synthetic cyclic somatostatin, respectively. Linear somatostatin (0.5 mg.) was without effect in two animals tested. Propionate (0.5 mmole per kilogram) and arginine (10 gm.) induced a rise in plasma insulin and GH, and glucagon was effectively blocked by cyclic somatostatin (0.5 mg.). Similarly, somatostatin inhibited glucose, and glucagon provoked GH and insulin secretory responses without affecting glucose or FFA levels. Somatostatin had no effect on the disappearance of injected glucagon. Finally, addition of somatostatin to incubation media prevented PGE promoted GH release, and suppressed cyclic AMP accumulation, although to a lesser extent, in sheep anterior pituitary pieces. In view of the large amounts required to suppress stimulated hormone release and the general lack of specificity of somatostatin, it is suggested that this peptide may have a functional role only in the release of hormones of the pituitary, where it could occur in relatively high local concentrations. Its inhibition of extrapituitary hormone secretion may be purely a pharmacologic effect that, nevertheless, suggests an interference with a step common to the secretory process of hormones.
Diabetes 1975 Sep
PMID:Studies on growth hormone secretion. VII. Effects of somatostatin on plasma GH, insulin, and glucagon in sheep. 16 76

The inhibitory actions of somatostatin (100 ng./ml.) on insulin release, stimulated by high glucose (20 mM), and on glucagon release, stimulated by arginine (15 mM), were studied with two in vitro systems: the isolated perifused rat islets prepared by the collagenase procedure and the isolated perfused rat pancreas. Suppression of arginine-induced glucagon release by glucose (20 mM) and glyceraldehyde (5 mM) was also assessed in both systems. With the perfused pancreas, somatostatin caused 32 per cent inhibition of glucose-mediated insulin release and inhibited arginine-induced glucagon release by 72 per cent. In the same system, glucose and glyceraldehyde were similarly potent inhibitors of arginine-induced glucagon secretion. In contrast to the isolated perfused pancreas, there was no significant somatostation suppression of glucose-induced insulin release or arginine-induced glucagon release whether the inhibitor was present prior to or was added during stimulation by glucose or arginine. Furthermore, glucose was only minimally active and glyceraldehyde ineffective in inhibiting glucagon secretion due to arginine in the perifusion system. The most plausible explanation for the difference in the endocrine response of islet cells in the two types of widely used in vitro systems is that the alpha and beta cells have lost inhibitory receptors in the plasma membrane as a result of the collagenase isolation technic.
Diabetes 1975 Nov
PMID:Comparison of alpha- and beta-cell secretory responses in islets isolated with collagenase and in the isolated perfused pancreas of rats. 17 Nov 90

With the use of isolated rat islet perfusion, levels of the islet cyclic adenosine 3' ,5' -monophosphate (cAMP) were compared with dynamic insulin secretion induced by tolbutamide and arginine. Tolbutamide elevated islet cAMP rapidly and augmented both glucose-induced islet cAMP levels and insulin secretion; arginine, however, did not elevate islet cAMP but did enhance glucose-induced insulin secretion. Since the latter result could have been modulated by cyclic guanosine 3' ,5' -monophosphate, this cyclic nucleotide was also measured and found to remain unchanged during stimulation of insulin secretion by arginine and a combination or arginine and glucose. Thus, the action of tolbutamide appears to be modulated in part by cAMP, whereas arginine appears to augment insulin secretion independently of cyclic nucleotides.
Diabetes 1976 Apr
PMID:Cyclic nucleotides in pancreatic islets. Tolbutamide- and arginine-induced insulin release. 17 55

Described here is a patient who had an islet cell carcinoma containing both glucagon (glucagonoma) and insulin (insulinoma). Complete removal of the tumor was possible. Immunoreactive glucagon (IRG) could be extracted from all parts of the tumor (approximately 50 mug./gm.) and was shown to be fully bioactive. Immunoreactive insulin (IRI) could be extracted only from one section of the tumor (approximately 30 mug./gm.). The clinical and biochemical manifestations of the disease were dermatitis, diabetes, weight loss, anemia, hypoaminoacidemia, and hyperketonemia. The diabetes was characterized by low or normal fasting blood glucose concentrations and by impaired glucose tolerance (Kg = 0.4). After complete removal of the tumor, the dermatitis cleared, the catabolic state changed into an anabolic state, blood amino acid concentrations increased, and blood ketone-body concentrations decreased. Fasting blood glucose concentrations, however, rose above 200 mg./dl., and glucose tolerance declined further (Kg = 0.15). Hourly blood sampling for 24 hours, intravenous and oral glucose tolerance tests, intravenous arginine and tolbutamide tolerance tests with serial determinations of IRG, IRI, and blood glucose were performed preoperatively and again two weeks and two months postoperatively. The results of these studies demonstrated marked abnormalities in the stimulation and suppression of glucagon and insulin release. In addition, they failed to demonstrate a glycemic effect on the chronically elevated glucagon concentrations in this patient, while identifying insulin as the dominant factor determining blood glucose homeostasis.
Diabetes 1977 Feb
PMID:An islet cell carcinoma containing glucagon and insulin. Chronic glucagon excess and glucose homeostasis. 19 71

Hyperglycemia, glucose intolerance, hyperinsulinemia and resistance to exogenous insulin were found in a 10-year-old Japanese boy diagnosed as having congenital generalized lipodystrophy. Studies on insulin receptors of circulating mononuclear leucocytes indicated that insulin-resistant diabetes combined with congenital generalized lipodystrophy may be due to disturbance of insulin binding to membrane receptors. No insulin-binding antibody or antibody that impairs insulin-receptor binding was found. Plasma glucagon showed an exaggerated response to L-arginine before treatment. After treatment with a controlled diet and an oral sulfonylurea (500 mg/day) for 4 weeks, there was improvement in the plasma glucagon response to L-arginine. Improvement in the hyperglycemia, hyperinsulinemia and acanthosis nigricans was also observed. On the other hand, on completion of a 7-day high-fat diet, a marked increase in serum free fatty acids, triglycerides and beta-lipoproteins was observed. The total plasma post-heparin lipolytic activity during the high fat diet was within the normal range. However, the level of protamine-inactivated activity was 3 times that of the control.
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PMID:Congenital generalized lipodystrophy with insulin-resistant diabetes. 20 64

The regional concentrations and in-vitro secretions of canine pancreatic polypeptide (cPP), insulin, and glucagon were studied. CPP is found predominantly in the uncinate process of the dog pancreas, whereas insulin and, more markedly, glucagon predominate in the body and tail of the pancreas. In-vitro secretion studies of pancreatic pieces indicate that dibutyryl cyclic AMP (dcAMP) alone can stimulate cPP release whereas glucose and arginine alone have no effect. Arginine, but not glucose, potentiates this stimulant effect of dcAMP. These studies suggest that the cAMP generating system may play a role in regulation of cPP secretion.
Diabetes 1978 Feb
PMID:Regional pancreatic concentration and in-vitro secretion of canine pancreatic polypeptide, insulin, and glucagon. 20 6

Ketotic, insulin-requiring diabetes mellitus and a severe peripheral neuropathy developed in a previously healthy 25-year-old man several days after he attempted suicide with rat poison containing N-3-pyridylmethyl N'-p-nitrophenyl urea. Study of islet-cell function ten months after ingestion showed a reduced disappearance rate of intravenous glucose and depressed C-peptide response to intravenous glucose when compared with a normal control but no impairment of glucagon release after intravenous arginine stimulation. Nerve conduction studies demonstrated severe sensory and mild motor neuropathy. Quadriceps capillary basement membrane thickness was in the diabetic range. Because at least 15 similar occurrences have been reported to the manufacturer, this agent appears to be diabetogenic in man, probably causing beta-cell destruction. Niacinamide, which can prevent glucose intolerance in both streptozocin- and alloxan-treated animals and prevents death in rats given this rodenticide, may be a useful antidote.
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PMID:Diabetes mellitus following rodenticide ingestion in man. 20 29

A new, spontaneously diabetic syndrome has been recognized in nonobese outbred Wistar rats of both sexes. The age at detection of first glycosuria has varied from 48 to 120 days, with a mean of 67 days. Eighteen rats have been studied, 14 untreated and four during and after cessation of insulin treatment. The affected animals have demonstrated a spectrum of severity, with hyperglycemia (252-732 mg./dl.), hypoinsulinemia (0-1 ng./ml.), and hyperketonemia. The severely ketotic rats, with total blood ketone body levels between 6 and 13 mM, showed rapid loss in weight and dehydration over one to six days. The moderately ketotic (1-5 mM) declined gradually in weight over 15 days, with marked polyuria and glycosuria. The stable rats, with ketonemia less than 1 mM, sustained their weights, polyuria, and glycosuria for longer than 40 days. A relative or absolute increase in plasma immunoreactive glucagon and elevated levels of free fatty acids and branched-chain amino acids were observed in relation to the severity of the syndrome. Intraperitoneal arginine or tolbutamide elicited no insulin response, but the glucagon response to arginine was exaggerated. Pancreatic insulin content was normal or moderately decreased. Light-microscopic examination of pancreases of ketotic animals at the end stage of the disease showed islets to be very small and rare, consisting virtually of non-beta cells. In stable and earlier ketotic rats, the islets were small, with reduction in beta-cell number and a striking inflammatory cell infiltration. Surviving beta cells showed variable degranulation. This model of spontaneous diabetes in nonobese rats displays insulin deficiency, glucagon excess, and ketosis, with a dramatic inflammatory lesion during active beta-cell destruction.
Diabetes 1977 Feb
PMID:The spontaneously diabetic Wistar rat. Metabolic and morphologic studies. 32 72

To investigate the development of diabetes mellitus in patients with thalassemia major, plasma glucose and immunoreactive insulin (IRI) levels following oral glucose and intravenous tolbutamide and glucose disappearance rates following intravenous insulin were measured in 10 patients before and during five years on a high transfusion program (HTP). Plasma immunoreactive glucagon (IRG) levels following oral glucose, intravenous insulin, and arginine were measured during the sixth year. Serial percutaneous liver biopsies were performed on seven patients. The oral glucose tolerance tests (OGAT) and mean peak IRI levels were normal in nine of 10 patients before HTP. After HTP was begun a progressive deterioration of OGTT occurred despite normal IRI levels. Following tolbutamide, the mean per cent fall in plasma glucose in the patients before HTP was significantly less than in controls (p less than 0.01) and similar to that of controls during five years of HTP in spite of higher than normal peak IRI levels. Of seven survivors after six years of HTP, three had normal OGTT and four had chemical diabetes; mean peak IRI levels were normal, but fasting IRG levels were significantly higher than in controls (p less than 0.05). In all seven patients, plasma IRG failed to increase following insulin-induced hypoglycemia and was significantly higher than in controls after arginine (p less than 0.01); after oral glucose, plasma IRG fell significantly below that of fasting only in the patients with chemical diabetes (p less than 0.03). Following intravenous insulin, the mean per cent fall in glucose before and during HTP was significantly less than in controls (p less than 0.01). Hemosiderosis and cirrhosis were present in all biopsied patients. Four patients died; two had chemical and two had nonketotic insulin-dependent diabetes. These data suggest that diabetes mellitus occurs frequently in patients with thalassemia on HTP and that insulin resistance and hyperglucagonemia, possibly due to cirrhosis, are important etiologic factors.
Diabetes 1977 Mar
PMID:Carbohydrate metabolism and pancreatic islet-cell function in thalassemia major. 32 76

Prostaglandin E(2) (PGE(2)) infusion in normal humans inhibited acute insulin responses to a glucose (5 g i.v.) pulse (response before PGE(2) = 593 +/- 104%; during PGE(2) = 312+/-55%; mean+/-SE, mean change 3-5 min insulin,% basal, P < 0.005). This effect was associated with a decrease in glucose disappearance rates (K(G) before PGE(2) = 0.73+/-0.07; during PGE(2) = 0.49+/-0.06%/min, P < 0.025). Acute insulin responses to arginine (2 g i.v.) were not affected by PGE(2) (response before PGE(2) = 592+/-164%; during PGE(2) = 590+/-118%; P = NS). Infusion of sodium salicylate (SS), an inhibitor of endogenous prostaglandin synthesis, augmented acute insulin responses to glucose in normals (response before SS = 313+/-62%; during SS = 660+/-86%; P < 0.001). In adult-onset diabetes with fasting hyperglycemia, SS restored absent acute insulin responses to glucose (20 g i.v.) pulses (response before SS = 5+/-6%; during SS = 97+/-24%; P < 0.005). This was accompanied by a fourfold augmentation in second phase insulin secretion (second phase before SS = 1,696+/-430%; during SS = 5,176+/-682%; change 10-60 min insulin, muU/ml.min,% basal, P < 0.001) and by acceleration of glucose disappearance rates (K(G) before SS = 0.56+/-0.06; during SS = 1.02+/-0.17%/min, P < 0.005). These findings uniquely demonstrate that (a) PGE(2) inhibits glucose-induced acute insulin responses and decreases glucose disposal in nondiabetic humans and (b) SS restores acute insulin responses, augments second phase insulin secretion, and accelerates glucose disposal in hyperglycemic, adultonset diabetics. It is hypothesized that endogenous PGE synthesis may play a role in defective insulin secretion and glucose intolerance in diabetes mellitus.
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PMID:A role for prostaglandin E in defective insulin secretion and carbohydrate intolerance in diabetes mellitus. 33 May 66


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