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)

Availability of specific cholecystokinin (CCK) receptor antagonists has the potential for contributing to delineation of the role of CCK in the development of pancreatitis and, perhaps, development of new therapeutic agents for treatment of the disorder. The purpose of this study was to evaluate the effect of a potent CCK receptor antagonist, CR 1409, on bile reflux pancreatitis. The opossum pancreatic duct enters the common duct in such a position that it is possible to ligate the common duct distal to the pancreatic duct, resulting in bile refluxing into the pancreatic duct and producing pancreatitis. CR 1409 was administered to opossums at the time of distal common duct ligation and at the time of cystic- and common ducts ligations. In a separate group, CR 1409 administration was begun 24 hours following onset of pancreatitis. Control experiments were performed, in which CR-1409 was not administered. Serum amylase, pancreas gland weights, inflammation, and systemic venous insulin, glucagon, and CCK concentrations were evaluated. Bile duct ligation resulted in significant hyperamylasemia, pancreas gland edema, inflammation, hyperglucagonemia, hypercholecystokinemia, and hypoinsulinemia. CR 1409, administered at the onset of pancreatitis, significantly decreased amylase concentrations, gland weight, and inflammation, when compared to control values. Hormonal changes associated with pancreatitis were also significantly altered by CR 1409 administration. When administered 24 hours following onset of pancreatitis, CR 1409 was not effective in altering the pancreatitis produced by bile duct ligation. The results suggest that CCK plays a permissive or contributory role in the inflammatory process and in associated hormonal changes during development of bile reflux pancreatitis in the opossum.
Pancreas 1991 May
PMID:The effect of the CCK receptor antagonist CR 1409 on bile reflux pancreatitis in the opossum. 171 73

Pancreatic procolipase, a protein cofactor for lipase, is activated by trypsin, with a simultaneous formation of colipase and a pentapeptide with the sequence Val-Pro-Asp-Pro-Arg (VPDPR). This peptide was found to significantly inhibit pancreatic protein secretion after intraduodenal infusion in pigs (2 mg/kg/h). The inhibition, amounting to 60%, occurred under base-line conditions as well as after stimulation with cholecystokinin (CCK)/secretin (1 U of each peptide/h/kg body wt). In contrast, intravenous infusion of VPDPR (0.2 mg/h/kg) did not affect pancreatic secretion. There was no significant change in the plasma levels of pancreatic polypeptide, insulin, glucagon, or glucose following intraduodenal infusion of VPDPR. It is concluded that the procolipase activation peptide might have an inhibitory function in pancreatic enzyme secretion mediated indirectly through a gut action. Therefore, the lipolytic enzymes of pancreas may also take part in the feed-back regulation of the pancreatic function. We suggest the name enterostatin for this novel regulatory peptide.
Pancreas 1991 Nov
PMID:Pancreatic procolipase activation peptide-enterostatin-inhibits pancreatic enzyme secretion in the pig. 178 Mar 22

Release of immature secretory granules rich in incompletely processed proinsulin has been proposed to explain the relative hyperproinsulinemia in type 2 diabetic and insulinoma patients because of a constant secretory drive resulting from hyperglycemia and autonomous secretion, respectively. To test this hypothesis, insulin secretion was stimulated by a combination of hyperglycemia (11 mmol/L clamp), intravenous (i.v.) tolbutamide (1 g), and i.v. glucagon (initial bolus 10 micrograms/kg body weight, maintenance infusion 2 micrograms/kg body weight per hour) for 3 h. Circulating IR-insulin and IR-C-peptide concentrations increased 89-fold and 14-fold over basal values, respectively, but IR-proinsulin concentrations increased only ninefold over basal values. Estimation of the amount of insulin secreted (based on deconvolution analysis of plasma C-peptide values) showed that approximately 76 +/- 21 U were secreted during the stimulation period. This amount is a significant proportion of pancreatic insulin content in normal humans. In molar terms, IR-proinsulin (integrated incremental response multiplied by metabolic clearance rate of proinsulin) relative to IR-C-peptide (= insulin) secretion (deconvolution analysis) was estimated to be equal or even lower than the known proportion in islets (0.22 +/- 0.05%). Thus, using a near-maximal stimulation of insulin secretion maintained long enough to cause release of amounts of insulin approaching the estimated pancreatic content, no preferential release of proinsulin was observed in normal humans. Therefore, the hyperproinsulinemia of type 2 diabetes and in insulinoma patients may be caused by additional defects in the proinsulin to insulin conversion process.
Pancreas 1991 Nov
PMID:Prolonged maximal stimulation of insulin secretion in healthy subjects does not provoke preferential release of proinsulin. 178 Mar 24

We recently reported that the secretion of insulin and glucagon by isolated murine islets is pulsatile and suggested that the pacemaker controlling these hormone oscillations is present in the islet. In the present study, we tested the hypothesis of an intrinsic islet neural controlling mechanism for the observed hormone pulsatility. Nerve blockade was attempted by infusion of tetrodotoxin (TTX) on a background of combined adrenergic and cholinergic blockade with atropine, propranolol, and phentolamine, (ATX). Because TTX acts by blocking Na+ channels, we also studied the effects of other cationic channel manipulations on the amplitude and frequency of the oscillations. The normal frequency and amplitude of glucagon and insulin oscillations were not affected by ATX. In contrast, TTX infusion increased the amplitude of insulin (198.6 +/- 20.9 vs. 507.2 +/- 62.8 pg/min, p less than 0.05, n = 4) and shortened the period from 5.03 +/- 0.26 to 3.33 +/- 0.0 min without affecting glucagon cycles. Whereas the Ca2+ ionophore A23187 had no effect on either hormone oscillation, the ATP-sensitive K+ channel blocker glyburide only increased the amplitude of insulin and decreased the amplitude of glucagon, without altering the frequencies. These data suggest that an intrinsic autonomously functioning islet nervous system is the pacemaker for the insulin oscillations and that the control of glucagon cycles differs from that of insulin.
Pancreas 1991 Nov
PMID:Effect of nerve blockade on pulsatile insulin and glucagon secretion in vitro. 178 Mar 25

We studied the cellular distribution of glucagon-like peptide-1 (GLP-1) in the pancreas and gut and the effects of GLP-1 and its truncated form, GLP-1(7-36) amide, on basal and stimulated insulin and glucagon secretion in the mouse. Immunofluorescence staining showed that GLP-1 immunoreactivity occurred within peripheral islet cells and in cells located mainly distally in the small intestine and in the entire large intestine. Double-immunostaining revealed that the GLP-1-immunoreactive cells were identical to the glucagon/glicentin cells. Experiments in vivo revealed that basal insulin secretion was stimulated by GLP-1(7-36) amide at the dose levels of 8 and 32 nmol/kg, and by GLP-1 at 32 nmol/kg. Furthermore, GLP-1(7-36) amide showed additive stimulatory influence with glucose (2.8 mmol/kg), the cholinergic agonist carbachol (0.16 mumol/kg), and the C-terminal octapeptide of cholecystokinin (CCK-8, 5.3 nmol/kg), when injected at 8 or 32 nmol/kg. In contrast, stimulated insulin secretion was unaffected by GLP-1. Moreover, the glucagon secretory responses to carbachol and CCK-8 were inhibited by GLP-1(7-36) amide but were unaffected by the entire GLP-1. We conclude that GLP-1(7-36) has the potential for being a modulator of islet hormone secretion.
Pancreas 1991 Mar
PMID:GLP-1 and GLP-1(7-36) amide: influences on basal and stimulated insulin and glucagon secretion in the mouse. 188 89

Pancreas transplantation, when successful, is a reproducibly effective method to normalize glycemia without the use of exogenous insulin treatment in patients with diabetes mellitus. Success rates for combined pancreas and kidney transplantation are approximately 70%, and patient survival rates are approximately 90% 1 yr postoperatively. Metabolic benefits of this procedure include normalization of levels of fasting plasma glucose and HbA1C. Glucose-induced insulin secretion and intravenous glucose tolerance are normalized. Improvements are also observed in glucose recovery after insulin-induced hypoglycemia and in glucagon secretion during hypoglycemia. Pancreas transplantation is also associated with normalization of kidney structure and both motor and sensory nerve function. However, no benefits have been observed with regard to pancreatic polypeptide secretion, kidney function, and the retinal pathology of diabetes mellitus. Pancreas transplantation has reached a point in its history where the operative technique and its ancillary medical therapy have been optimized. Improvement in the rates of success, morbidity, and mortality will probably depend on improvement in immunosuppressive drugs and the physical condition of the recipients themselves. The time is at hand when we need to carefully consider whether it is ethical and advisable to make pancreas transplantation available to individuals who have fewer chronic complications of diabetes mellitus. Future studies of pancreas transplantation must incorporate more rigid experimental controls than have been used in the past to better assess the relative merits of this procedure.
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PMID:Pancreas transplantation in humans with diabetes mellitus. 193 15

We have investigated the influence of non-insulin-dependent diabetes on the regulation of somatostatin secretion from the pancreatic D cell. These results were compared with the concomittantly measured secretory responses from A and B cells. Rats were rendered non-insulin-dependent diabetic by neonatal injection of streptozotocin (STZ). Secretion was studied in perfused pancreas at 6-10 weeks of age. At this age, STZ rats were mildly hyperglycemic, their nonfasting blood glucose being 9.0 +/- 0.8 vs. 5.6 +/- 0.2 mM in control rats. In perfused pancreas from the latter rats, high glucose, i.e., 16.7 mM, stimulated somatostatin secretion but completely failed to do so in STZ rats. Arginine (in the presence of low glucose, i.e., 3.3 mM) moderately stimulated somatostatin secretion in controls but fourfold more in STZ rats. Preperfusion with high glucose markedly potentiated subsequent arginine-induced somatostatin secretion in controls but failed to do so in STZ rats. Basal glucagon release was inhibited by ambient high glucose in control and STZ rats alike. Arginine-induced glucagon release was profoundly inhibited both by ambient and previous exposure to glucose in controls but only slightly and nonsignificantly in STZ rats. The insulin response to high glucose in controls was reduced by 90% in STZ. The insulin response to arginine (in the presence of low glucose) was 3.3-fold enhanced in STZ. Ambient and previous high glucose markedly enhanced arginine-induced insulin secretion in controls but only moderately so in STZ rats. We conclude that already mild hyperglycemia is associated with marked D-cell insensitivity to glucose that is qualitatively similar to A- and B-cell insensitivity.
Pancreas 1990 May
PMID:Abnormal regulation by glucose of somatostatin secretion in the perfused pancreas of NIDDM rats. 197 41

The BB/W strain of rats develop spontaneous insulin-dependent diabetes. Diabetic BB/W rats have a marked insulinopenia and greatly diminished levels of insulin in their pancreas. Using a radioimmunoassay for rat pancreatic polypeptide (PP), we have examined the content of PP in extracts of the total pancreas and also the regional PP concentration of the three pancreatic lobes. Radioimmunoassays for glucagon, somatostatin (SRIF) and insulin were also made on these extracts. Compared with nondiabetic BB/W rat pancreas, pancreatic extracts from severely diabetic BB/W rats contained 30% as much PP, 31% as much glucagon, 19% as much SRIF, and 0.5% as much insulin. The rat PP radioimmunoassay was used to determine the elution pattern of PP-like antigens in gel chromatography fractions and to measure in vitro secretion of PP from perifused pancreatic slices obtained from diabetic and nondiabetic animals. PP-like immunoreactivity was observed in two zones in the elution from the gel columns when extracts from normal or diabetic rats were chromatographed. The major zone of immunoreactivity eluting at the volume expected for intact monometric rat PP accounted for 67% of the PP-like immunoreactivity in the case of nondiabetic rats and greater than 80% of the PP-like immunoreactivity found in extracts from severely diabetic rats. The minor zone of PP-like immunoreactivity eluted at a volume similar to the position of tetradecapeptide SRIF contained the remainder of detected PP-like immunoreactivity. Tissue slices from diabetic rats secreted more PP and glucagon than slices from nondiabetic rats when slices were perifused with a medium containing leucine, carbachol, and cholecystokinin, even though diabetic pancreas has smaller amounts of PP, glucagon, SRIF, and insulin. Stimulated insulin secretion was virtually absent when tissue slices from diabetic rats were perifused. These results indicate that in the BB/W diabetic rat: (a) pancreatic glucagon, PP, and SRIF are moderately decreased and insulin levels are drastically reduced, (b) lower levels of degraded or low molecular weight form of immunoreactive PP occurs in the diabetic rat pancreas compared to the normal rat, (c) the diabetic pancreas secretes more PP and glucagon and much less insulin than pancreas from nondiabetic rats when perifused under stimulating conditions. The diabetes occurring in the BB/W appears to be a severe type I diabetes characterized by reduced content of insulin, glucagon, SRIF, and PP in the pancreas of these animals. However, secretion of glucagon and PP were not reduced in this in vitro system.
Pancreas 1990 Nov
PMID:Pancreatic polypeptide and other pancreatic hormones in spontaneously diabetic BB/W rats. 198 Jul 35

A rare case of cystic pancreatic endocrine tumor is presented, and the literature is reviewed. The patient was initially misdiagnosed as having a pancreatic pseudocyst, and that condition was managed accordingly. Persistence of the cystic lesion and reoperation led to the correct diagnosis and management. The neoplasm stained positive for glucagon and pancreatic polypeptide, but there were no clinical abnormalities that suggested hyperfunction. All cystic lesions of the pancreas should undergo biopsy at operation, to avoid an erroneous diagnosis of benign pseudocyst. Neoplastic lesions should be resected, not internally drained.
Pancreas 1990 Mar
PMID:Pancreatic cystic endocrine neoplasms. 215 58

Seasonal changes in pancreatic insulin and glucagon were investigated in the little brown bat (Myotis lucifugus). Pancreatic protein content increased 21% from the nonhibernating state in June compared to the nonhibernating or early hibernating state in late October, and then decreased 50% between October and the months of deep hibernation. The content of insulin and glucagon increased from June to October, and both hormones further increased during hibernation, when a fall in pancreatic protein content occurred. The concentration of both insulin and glucagon increased from October to February. Of note, the insulin concentration progressively increased during deep hibernation from February to April, whereas the glucagon concentration remained constantly elevated throughout this time interval. The persistent elevation of pancreatic glucagon during hibernation may be related to its role in counterregulation and carbohydrate homeostasis during fasting. The elevation of pancreatic insulin, and its further increase during hibernation, is less clear but may be hypothesized to provide a rapidly releasable storage pool required for immediate secretion during arousal, possibly to prevent a hyperosmolar state.
Pancreas 1990 May
PMID:Seasonal changes in pancreatic insulin and glucagon in the little brown bat (Myotis lucifugus). 218 57


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