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)

Serum GIP, insulin, and glucose concentrations were determined during a standard oral glucose tolerance test in 80 individuals, 45 of whom were normal and 35 of whom had adult-onset diabetes mellitus according to USPHS criteria. As a group, the diabetics had fasting hyperglycemia (219 +/- 17 mg./dl.) and, in response to glucose, displayed a peak serum glucose of 373 +/- 23 mg./dl. and sustained hyperglycemia (315 +/- 24 mg./dl.) at 180 minutes. There were no statistically significant differences in absolute serum insulin levels between the two groups. However, insulin secretion was delayed, IRI increments were smaller, and the IRI concentrations were inappropriately low for the simultaneous serum glucose concentrations in the diabetics at every time interval tested. Mean fasting serum GIP was 335 +/- 30 pg./ml. in the diabetics as against 262 +/- 15 pg./ml. in normal individuals (p less than 0.025). After the ingestion of glucose, diabetics had significantly higher (p less than 0.001) mean serum GIP levels between five and 120 minutes. By 180 minutes, serum GIP levels remained above fasting in both groups, but the diabetics had higher than normal serum concentrations (p less than 0.05). Peak serum GIP concentrations, which occurred at 30 minutes in both groups, were 1,376 +/- 106 and 806 +/- 75 pg./ml. in the diabetics and normals, respectively (p less than 0.001). Total integrated serum GIP was also greater in diabetics than normals (140,852 +/- 14,208 vs. 64,602 +/- 8,719 pg.-min./ml.-1, p less than 0.001). The higher serum GIP concentrations observed following glucose ingestion in diabetics could not be attributed to obesity or age. We conclude that both fasting and glucose-stimulated GIP concentrations are higher than normal in obese adult-onset diabetics. The significance of this observation is uncertain. However, since our current understanding suggests the GIP may be an important enteric signal for the release of insulin in man, and because GIP has been shown to stimulate the release of immunoreactive glucagon, GIP may play a role in the pathogenesis of diabetes mellitus.
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PMID:Gastric inhibitory polypeptide (GIP) in maturity-onset diabetes mellitus. 97 1

Somatostatin, a peptide isolated from ovine hypothalami, prevents growth hormone secretion in vivo and in vitro. Moreover, somatostatin interferes with the secretion of various other hormones: TSH insulin, glucagon, gastrin, VIP and GIP. Under certain conditions a blunting effect on the secretion of prolactin and ACTH can be demonstrated.
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PMID:[Somatostatin -- a review (author's transl)]. 126 5

1. The primordial GRF may have arisen quite early in evolutionary history, at or prior to (i.e. should immunoreactivity data be confirmed in invertebrates) the appearance of jawed vertebrates (Gnathostomates). A common evolutionary pathway using gene duplication may have been utilized to generate the GRF super-family of peptides. As most members of this peptide superfamily are produced in the gastrointestinal tract, the question is posed whether the GRF may have similar origins. 2. It is suggested that the GRF superfamily has two major branches: a) GRF; PRP/PACAP; VIP/PHI; secretin and b) Glucagon/GLP-1/GLP-2. GIP is likely to be a member of the glucagon branch. The two branches may be attributable to gene duplication encoding an ancestral molecule. These gene duplications are likely to have occurred prior to the evolution of vertebrates (conservatively 400-500 million years ago, and possibly 1 billion years ago). It is probable that peptides homologous to GRF, VIP and glucagon will be isolated from invertebrates. These invertebrate sequences will shed further light upon the evolution of this peptide superfamily. 3. Throughout the GRF superfamily, amphiphilic alpha-helical secondary structures represent preferred bioactive conformations. It is assumed that stable, ordered secondary structures conferring enhanced ligand-receptor interactions were conserved due to selective pressures. 4. It is well documented that hypothalamic GRF stimulates adenohypophyseal GH secretion in a variety of species. Thus far, the physiological effects of GRF have been attributed thus to the elevation of GH, and possibly also IGF-I. Recent data suggests a more liberal view; that GRF may also have direct actions in fetal/placental development, reproduction and immune function. Furthermore these direct effects may be mediated via GRF from either hypothalamic or extrahypothalamic (e.g. placenta, testes, ovary, leukocyte) sources. In conclusion, a great wealth of information has accumulated since the discovery of GRF. Examination of the GRF peptide superfamily from an evolutionary perspective has revealed new insights into the synthesis, processing, degradation, conformation and activities of these molecules. Knowledge obtained from these evolutionary comparisons has also become particularly useful in contemporary peptide drug design, which may be liberally viewed as a form of 'artificial evolution' (i.e. the selective pressure being clinical/veterinary requirements for more potent, long-acting GRF analogs).
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PMID:Evolution of the growth hormone-releasing factor (GRF) family of peptides. 129 Sep 54

To clarify changes in gastric acid and gut hormone secretion after pylorus-preserving pancreaticoduodenectomy (PPPD), an experimental study was performed using a model of pylorus-preserving duodenectomy in dogs previously provided with Heidenhain pouch (HP). The duodenectomy involves resection of the duodenum and 10 cm of the proximal jejunum preserving 2 cm of juxtapyloric duodenum and round-shaped duodenal wall around pancreatic papilla. Reconstruction was done by anastomosing the rho-shaped jejunal loop to gallbladder, juxtapyloric duodenum and peripapillar round-shaped duodenal wall with ligation of the common bile duct. For these dogs, intravenous glucose tolerance test (IVGTT), oral glucose tolerance test (OGTT), meal ingestion test (TM) and histological studies of pancreatic specimen obtained at autopsy were performed investigating pancreatic, gastric acid and gut hormone secretion. Preservation of endocrine and exocrine pancreatic secretion after operation demonstrated our experimental model to be adequate for evaluation of the factor of duodenectomy in PPPD on gastric acid and gut hormone secretion avoiding the influences of changes in pancreatic secretion. Postprandial gastric acid secretion from HP did not change significantly after operation. Postprandial secretion of gastrin, glucagon, GIP and enteroglucagon did not alter significantly after operation. These results indicated that in the clinical PPPD procedure, preservation of more than 2 cm of duodenum from the pylorus produced neither postprandial gastric acid hypersecretion, which might be cause of postoperative stomal ulcer, nor any change of related gut hormone secretion.
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PMID:An experimental study on the gastric acid and gut hormone secretion after pylorus preserving duodenectomy in dogs. 135 8

1. The incretin effect (i.e. the difference between the insulin response after oral and i.v. glucose) is reduced in type 2 diabetes although GIP secretion is normal or exaggerated. This suggests an insensitivity of the diabetic B-cell to GIP. However, it could also indicate the lack of another not yet defined "incretin". 2. While CCK is a potent incretin in rats and dogs, physiological concentrations of this hormone do not stimulate insulin secretion in man in presence of elevated blood levels of glucose or phenylalanine in the physiological range. It also does not interact with GIP. 3. Glucagon-like peptide I (7-36) is a potent glucose-dependent stimulator of insulin secretion in animals and man. Preliminary data suggest release after oral glucose despite localization of the GLPI containing cells predominantly in the ileum and colon. More data are needed before GLPI (7-36) can be regarded as a physiological incretin and its role in type 2 diabetes assessed.
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PMID:Entero-insular axis and diabetes mellitus. 149 Jun 80

After ingestion of glucose both GIP (gastric inhibitory polypeptide, glucose-dependent insulinotropic polypeptide) and GLP-1(7-36amide) (glucagon-like polypeptide-1, 7-36amide) may play a physiological role in augmenting insulin release. Their insulinotropic effect was compared in isolated rat islets after 24-h maintenance in tissue culture (11 mmol l-1 glucose). Ten islets per vial were then incubated in Krebs-Ringer-Hepes buffer for 30 min; insulin was measured radioimmunologically. Both hormones were always compared in the same experiment. At 16.7 mmol l-1 glucose both GIP and GLP-1(7-36amide) 2 x 10(-10) mol l-1 significantly increased insulin release; 10(-10) mol l-1 of either hormone had no significant effect. The response at 10(-9) and 10(-8) mol l-1 was similar for both; at 4 x 10(-10) mol l-1 GLP-1(7-36amide), however, was clearly more effective than GIP. At low glucose (2.8 or 5.0 mol l-1) no significant differences were found. A concentration of 10(-8) mol l-1 of both hormones was slightly stimulatory. At 8.3 mmol l-1 glucose, 10(-9) mol l-1 GLP-1(7-36amide) was 60% more effective than GIP (4.8 +/- 0.4 vs. 3.0 +/- 0.4, n = 13, P less than 0.005), the response to 10(-8) mol l-1 was similar. These data show comparable effects of high concentrations of GIP and GLP-1(7-36amide) on glucose-induced insulin release; at presumably physiological concentrations, however, GLP-1(7-36amide) was clearly more effective. The combination of the two peptides was not more than additive, suggesting that they act via the same final mechanism.
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PMID:Comparison of the effect of GIP and GLP-1 (7-36amide) on insulin release from rat pancreatic islets. 158 39

The secretion of pancreatic and gastrointestinal hormones in the basal state and after nutrient stimuli (50 g glucose, 50 g protein, or 30 g triglyceride administered on separate occasions) was assessed in ten previously type-1-diabetic patients after successful combined kidney and pancreas transplantation (systemic venous drainage). Fasting values were compared to matched non-diabetic kidney-transplanted patients and related to kidney function (endogenous creatinine clearance) and to the type and dosage of immunosuppressive medication. In the fasting state, only IR insulin concentrations were higher in pancreas-kidney-transplanted patients (by 88%; P = 0.001) than in the kidney graft recipients. There were significant inverse correlations of plasma C-peptide, GIP, and gastrin immunoreactivity to endogenous creatinine clearance (kidney function). In response to nutrients, insulin secretion (IR insulin, C-peptide) was significantly stimulated by glucose, and - to a lesser degree - also by protein. Pancreatic glucagon was suppressed by glucose and stimulated by protein ingestion. GIP was raised after glucose and triglyceride more than after protein (P = 0.0003). GLP-1 immunoreactivity was stimulated by all nutrients, with a tendency towards higher responses to protein and fat (P = 0.06). Gastrin was mainly raised by protein. In conclusion, the overall pattern of pancreatic and gastrointestinal hormone release is normal in patients after combined pancreas-kidney-transplantation, but there are some peculiarities due to (a) systemic venous drainage of the pancreas graft (elevated fasting IR insulin) and (b) impaired kidney function (negative correlation of fasting plasma values to endogenous creatinine clearance for C-peptide, GIP, and gastrin).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Basal and nutrient-stimulated pancreatic and gastrointestinal hormone concentrations in type-1-diabetic patients after successful combined pancreas and kidney transplantation. 160 Mar 30

Pancreatic endocrine function was studied in 50 patients with cystic fibrosis (CF) and 15 healthy controls by measuring glucose, insulin, C-peptide, glucagon and gastro-inhibitory polypeptide responses to an oral glucose tolerance test (OGTT). Biochemical and clinical parameters were also measured, including glycosylated hemoglobin A1, serum immunoreactive trypsin, fasting urinalysis, pulmonary function, percentage body fat and 3-day dietary records. According to National Diabetes Data Group (NDDG) criteria, 6 CF patients had impaired glucose tolerance (ICF), with elevated serum glucose concentrations and reduced and delayed insulin secretion compared with control (CON) subjects, although none were overtly diabetic. Although the remaining 44 CF patients (NCF) did not meet NDDG criteria for impaired glucose tolerance, mean area under the concentration curve (AUC) for glucose was greater than control values and AUC for insulin diminished. HbA1 levels in the 2 CF groups were greater than that of controls subjects, but there was little difference between ICF and NCF groups. C-peptide levels paralleled those of insulin for the 3 groups throughout OGTT. There was little difference in GIP secretion between groups, and the enteroinsular axis was intact in the control and NCF groups and slightly increased in the ICF group. Basal glucagon concentrations and AUC for glucagon during OGTT were similar for the 3 groups, but glucose-induced glucagon suppressibility i.e., basal to nadir change in each subject, was reduced in the ICF group. Serum IRT concentration was significantly lower in the ICF and NCF groups compared to control subjects, and was lowest in the ICF group. A strong correlation was observed in the ICF group between FEF25-75 and AUC for insulin, as well as HbA1 level and AUC for glucose. The prevalence of impaired glucose tolerance in 50 CF patients was 12%. Despite extensive comparisons of biochemical and clinical parameters with endocrine function in this population, we were unable to define reliable criteria for predicting glucose intolerance.
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PMID:Postprandial hyperglycemia and pancreatic function in cystic fibrosis patients. 184 15

The effects of glucose and GIP on glucagon secretion were studied in perifused microdissected murine pancreatic islets. Glucagon levels were determined in effluent samples collected at 1-min intervals by radioimmunoassay using the glucagon-specific antibody, 30 K. There was no significant difference in the total amount (7740 +/- 212 pg vs 8630 +/- 36 pg, n = 10) of glucagon secreted over a 20 min period when the glucose concentration was alternately shifted between 5.5 mM and 11.1 mM, respectively. However, 22.2 mM glucose profoundly suppressed glucagon secretion. The suppressive effect of high glucose on glucagon release was partially, yet significantly, reversed by the presence of GIP, as glucagon secretion increased from a non-detectable level at 22.2 mM glucose alone to 10,175 +/- 145 pg, n = 10 (P less than 0.01). The glucagonotropic effect of GIP was dose-dependent in the range of 2 x 10(-9) - 2 x 10(-7) M, at 11.1 mM glucose. Our data show that GIP is able to substantially reverse the suppressive effect of a high glucose load on glucagon secretion.
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PMID:Influence of gastric inhibitory polypeptide (GIP) and glucose on the regulation of glucagon secretion by pancreatic alpha cells. 203 23

Adult onset nesidioblastosis (AON) is an extremely rare entity associated with hypersecretion of insulin. Previous reports have demonstrated that the somatostatin analog, Sandostatin (SMS), will control the clinical symptoms induced by infantile nesidioblastosis. We hypothesized that insulin, C-peptide, and secondary peptide secretion from AON is provocable. We also hypothesized that SMS would suppress both basal and provoked primary and secondary peptide secretion in AON. To test this hypothesis, in a patient with AON, 13 gut peptide levels were determined at set intervals during provocative testing with a test meal, a calcium infusion, a secretin bolus, and a glucagon bolus. These tests were repeated under the influence of SMS. Insulin, C-peptide, and pancreatic polypeptide (PP) levels were elevated in the basal state. SMS suppressed all three peptides (mean 68%) (p less than 0.05). Basal fasting glucose rose by 65%, and glucose ratios were raised throughout all four tests. Insulin:glucose ratios decreased during SMS therapy. Insulin and PP secretion was increased by all four provocative tests (mean 458% and 665% above baseline, respectively). C-peptide was provoked by three tests (mean 204%). Peptides with normal basal values were also provocable. GRP and glucagon were provoked by secretin stimulation (182%, 186%, respectively). Calcium infusion stimulated CIP release by 372%. SMS suppressed the peak provoked peptide levels in all positive provocation tests (p less than 0.05). Peak provoked insulin values were decreased by 59%, C-peptide by 75%, and PP by 92%. Peak provoked glucagon, CRP, neurotensin, and GIP levels were decreased by 20%, 65%, 51%, and 73%, respectively. The patient has been maintained on SMS (25 micrograms bid) for 1 yr and has shown decreased insulin levels, normal glucose levels, and, at 1 yr, leads an asymptomatic normal life. SMS is able to suppress primary and secondary peptide secretion in both the fasting and provoked state. The long-term efficacy of SMS may be predicted by its ability to suppress primary peptide release during peak provocation.
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PMID:Adult onset nesidioblastosis: response of glucose, insulin, and secondary peptides to therapy with Sandostatin. 240 44


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