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)

Glucose tolerance and insulin and glucagon secretion were examined sequentially during 6 months of calorie and carbohydrate restriction in an obese, recent-onset, ketosis-resistant diabetic adult. The subject was then followed for 9 additional months, during which some weight was regained. Fasting plasma glucose levels returned to normal after 6 week of calorie restriction and remained normal during periods of carbohydrate refeeding. Normalization of 2-h plasma glucose concentrations after a standard oral carbohydrate load required 5 months, and glucose disposal after an iv glucose load did not return to normal until the end of the study. Insulin secretion in response to oral glucose reached maximal levels during the first months of weight reduction and then decreased as glucose tolerance continued to improve. Acute phase insulin release in response to iv glucose gradually increased throughout the study. Glucagon stimulation by iv arginine and suppression by iv glucose also returned to normal levels slowly over several months. Abnormalities in glucose tolerance and glucoregulatory hormone secretion of ketosis-resistant diabetes are totally reversible with prolonged dietary therapy. Reduction in tissue resistance to the action of insulin also appeared to be of major importance in the recovery of normal glucose tolerance in this subject.
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PMID:Normalization of insulin and glucagon secretion in ketosis-resistant diabetes mellitus with prolonged diet therapy. 11 19

The hyperglucagonemia that occurs in vivo in animals made diabetic with alloxan or streptozotocin is not suppressed by high glucose but is suppressed by exogenous insulin. These observations together with other studies suggested that insulin-dependent glucose transport and metabolism by the alpha-cells serves as the primary mechanism controlling glucagon secretion. This hypothesis was tested in the present investigation. The possible interactions between glucose, insulin, and a mixture of 20 amino acids at physiological proportions were examined in the isolated-perfusin diabetic rats. Release of insulin and glucagon were used as indicators of theta-cell and alpha-cell function. According to rigid criteria the diabetic animals entering the study were severely diabetic. It was found that in vitro: (a) basal glucagon release (measured in the absence of an alpha-cell stimulus or inhibitor) was extremely low, even lower (i.e. 10%) than the basal rates seen in controls; (b) the alpha-cells of alloxanized- and streptozotocin-treated rats responded with a biphasic glucagon release to stimulation by an amino acid mixture; (c) this alpha-cell response was reduced after both streptozotocin and alloxan; (d) glucose at 5 mM was a potent inhibitor of amino acid-induced glucagon secretion in both types of experimental diabetes; (e) in alloxan diabetes alpha-cell stimulation by amino acids can be curbed by exogenous insulin, whereas glucagon secretion by the perfused pancreas of streptoxotocin diabetic rats appeared to be resistant to insulin action. The data indicate that the modulation of glucagon secretion by glucose in vitro is indipendent of insulin and that other unknown factors extrinsic to the pancreatic islets are responsible for the hyperglucagonemia observed in vivo.
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PMID:Insulin and glucose as modulators of the amino acid-induced glucagon release in the isolated pancreas of alloxan and streptozotocin diabetic rats. 12 28

Everted intestinal rings from partially starved rats accumulate the nonmetabolized amino acid 1-amino-cyclopentane-5-carboxylic acid (ACPC) at an enhanced rate. Plasma glucagon concentrations were found to be markedly elevated in these partially starved rats as well as in rats with experimentally induced diabetes, a condition previously shown to be associated with augmented intestinal uptake of amino acid. Treatment of partially starved rats with repeated injections of glucagon-binding antiserum prevented increased ACPC uptake of intestinal rings. Chronically elevated plasma glucagon levels may participate in the mechanism of the functional changes in the intestine in partial starvation.
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PMID:Treatment with glucagon-binding antibodies alters the intestinal response to starvation in the rat. 12 36

Islet isografts were injected into the portal veins of rats made diabetic with streptozotocin. The isografts normalized not only plasma glucose and insulin levels but also the elevated plasma immunoreactive glucagon level. The in vitro basal insulin secretion and prompt sensitivity to glucose were shown directly by perfusing isolated livers containing transplanted islets. In vitro glucagon secretion to an arginine stimulus could not be demonstrated, although it would have been expected demonstrated, although it would have been expected in normal islets. Thus, it appears that insulin derived from transplanted islets is capable of correcting endogenous hyperglucagonemia and of ameliorating the effects of experimental diabetes while transplanted islet glucagon secretion is relatively suppressed.
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PMID:Islet transplantation into rat liver: in vitro secretion of insulin from the isolated perfused liver and in vivo glucagon suppression. 13 Oct 32

One hour following intravenous streptozotocin, rat pancreases were perfused in situ, and , in contrast to saline-injected controls a marked decrease of insulin secretion was observed. In these streptozotocin-treated animals, baseline glucagon secretion was enhanced when the perfusate glucose concentration was either 80 mg./100 ml. or 300 mg./100 ml. In addition there was hypersecretion of glucagon in response to arginine. Exogenous insulin (20,000 muU./ml.) could suppress glucagon secretion when endogenous secretion was plentiful. Baseline and arginine-stimulated glucagon secretion of the streptozotocin treated animals was not suppressed by large amounts of glucose and insulin to the degree seen in control animals. The glucagon rise in response to an abrupt fall of glucose from 80 mg./100 ml. to 25 mg./100 ml. was not significantly higher in the control group than in the streptozotocin group. The results seen with epinephrine were in sharp contrast to those found with arginine. Epinephrine-stimulated glucagon secretion was not enhanced in the streptozotocin group. In addition, epinephrine-induced secretion could be suppressed by exogenous insulin in both the control and streptozotocin groups. The differences may be secondary to differences of endogenous insulin secretion. The present results are compatible with the hypothesis that local insulin secretion can exert a significant suppressive effect upon the alpha cell and that the inhibition of glucagon secretion by glucose is partially mediated by this mechanism. Furthermore, anomalous local insulin secretion may contribute to the abnormal glucagon secretion of diabetes mellitus.
Diabetes 1976 Apr
PMID:Glucagon secretion from the perfused pancreas of streptozotocin-treated rats. 13 25

In more than 1,000 radiological and endoscopic examinations of the smooth muscle hollow organs of the upper intestinal tract, crysalline glucagon (0.2 to 0.5 mg., average dose 1 u/kg. body weight given at a single intravenous injection) resulted in a significant relaxation and reduction of peristalsis. This effect was less marked in the colon and recto-sigmoid. In five patients with colonic diverticulosis it had no effect. In 150 patients it was found that the onset of hypotonia after injection of glucagon increases from proximal to distal, the duration of maximal reduction in peristalsis decreasing distally. Glucagon is indicated for reducing the tone of smooth muscle hollow organs in order to judge their elasticity and to distinguish between functional and organic causes of a stenosis or increased size of folds. The rapid onset of peristaltic inhibition makes various diagnostic and therapeutic endoscopic procedures simpler or even possible. Compared with the usual atropin-like antispasmodics, glucagon has the advantage of being free from side effects apart from transient hyperglycaemia. Diabetes mellitus requiring insulin is a (relative) contra-indication to the use of glucagon.
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PMID:[The use glucagon for endoscopic and radiological examination of the gastrointestinal tract (author's transl)]. 13 38

Recovery from diabetes was observed in streptozotocin-treated mice that received subcutaneous, isogeneic transplants of duct-ligated pancreas. Transplants excised from recovered hosts contained both immunoreactive insulin (IRI) and glucagon (IRG), indicating that both A and B cells capable of hormone storage were present. The IRI content in transplants, although only one sixth of that transplanted 6 wk earlier, was still 21/2 times greater than that in the host pancreas and was inversely related to the plasma glucose of the recipient during and after recovery. The IRI content in the transplant added to that in the host pancreas totaled 13% of the IRI found in the normal mouse pancreas, which sufficed for over-all recovery from diabetes but was insufficient to provide normal glucose tolerance and insulin response to a major glucose challenge. The abnormally high content of glucagon noted in the pancreas of hyperglycemic, sham transplanted mice was reduced by one-half in the pancreas of those transplanted mice returning to normal plasma glucose and insulin. Thus, the insulin content of the transplant was important to the recovery of isografted mice, but in addition, and perhaps as a consequence of recovery, there was a slight increase in the insulin storage capacity of the host pancreas and a marked reduction of glucagon compared to the content of these hormones in the pancreas of hyperglycemic, sham transplanted mice.
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PMID:Subcutaneous, isogeneic transplantation of duct-ligated pancreas in streptozotocin diabetic mice: relationships between recovery and hormone contents in transplants or host pancreas. 13 45

Fasting blood glucose (FBG), serum immunoreactive insulin (IRI), plasma immunoreactive glucagon (IRG), body weight, and caloric intake were measured in long-term islet-isografted rats eight to 10 months following intraperitoneal islet transplantation in in age-matched, sham-operated, concurrently followed normal and diabetic controls. Islet recipients had normal body weights, but they were significantly polyphagic, hyperinsulinemic, and hyperglucagonemic when compared with normals. Fasting blood glucose levels were reduced by 10 per cent. Several factors may be related to the occurrence of these abnormalities in long-term islet-isografted rats, including (1) the mass of islets transplanted, (2) the age of donor tissue, (3) the heterotopic location of islet grafts, and (4) the lack of normal innervation of transplanted islet cells.
Diabetes 1976 Oct
PMID:Hyperinsulinemia and hyperglucagonemia following pancreatic islet transplantation in diabetic rats. 13 3

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.
Diabetes 1976 Nov
PMID:Metabolic and morphologic studies in intraportal-islet-transplanted rats. 13 76

It has been suggested that the hyperglucagonemia observed in diabetic animals and man may be due to an impairment of glucose uptake and metabolism by the alpha-cells resulting in a decreased production of ATP. To test this hypothesis glucose, ATP, glucagon, and insulin were measured in pancreatic islets of normal and alloxan or streptozotocin diabetic rats. Two experimental approaches were used. In the first, the pancreas was perfused in vitro for assessing insulin and glucagon release due to 10 mM amino acids with and without 5 mM glucose. These perfusions were performed in the presence and absence of insulin. After perfusion, the pancreas was frozen and processed for analysis of islet glucose, ATP, insulin, and glucagon content. The second approach was to investigate the islet sucrose, urea, and glucose spaces together with ATP, insulin, and glucagon content in vivo in normal and in insulin-treated and untreated streptozotocin diabetic rats. Perfusion of the pancreas in vitro with 5 mM glucose resulted in higher glucose content of normal islets than in alloxan and streptozotocin diabetic islets. Similarly in the in vivo studies, the intracellular glucose space of the streptozotocin diabetic islets was 30% the value found in normals. In the in vivo experiments, despite the relatively small intracellular glucose space of alpha-cell islets, the ATP content of these islets was only 15-20% lower than the ATP content of normal islets. In the in vitro experiments, perfusion with glucose resulted in ATP contents of alpha-cell islets and of normal mixed alpha-beta-cell islets which were indistinguishable. However, the ATP content of alpha-cell islets was maintained for prolonged periods in the absence of glucose in contrast to mixed islets, composed primarily of beta-cells, in which the ATP level decreased by 45% when glucose-free medium was perfused for sustained periods. Finally, insulin infused in high concentrations or administered to the diabetic animal had no effect on the glucose spaces or the ATP contents of normal or alpha-cell islets. It can be calculated that in vivo the intracellular glucose level of islets from streptozotocin treated rats is approximately 15 mM. Since in normals an extracellular glucose concentration of this magnitude inhibits stimulated glucagon release completely, it would seem unlikely that a lack of intracellular glucose is the cause of the apparent glucose "blindness" of the alpha-cells in diabetes. In fact, in perfusion studies as little as 2.5 mM free intracellular glucose was sufficient to suppress glucagon secretion from diabetic alpha-cells. The results of the ATP measurements clearly eliminate a possible energy deficit of diabetic alpha-cells as cause of the apparent glucose resistance of alpha-cells.
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PMID:Glucose and ATP levels in pancreatic islet tissue of normal and diabetic rats. 13 53


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