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

With the advent of radioimmunoassay and immunocytochemical methods, the peptides of the gastrointestinal tract have been identified and measured. Gastrinoma and insulinoma syndromes have been wall characterized. The pancreatic cholera syndrome and some of the evidence that the major manifestations of this disease may be mediated by vasoactive intestinal peptide have been re-examined. Pancreatic polypeptide seems to be an ideal peptide for study of vagal-cholinergic mechanisms that regulate hormone release; it also appears to be a tumor marker for several types of pancreatic endocrine tumors, particularly those of pancreatic cholera. Secretin and cholecystokinin are important regulators of pancreatic exocrine secretion and have been used to test pancreatic function, but there is little evidence that they account for clinical disease. Glucagon-secreting tumors produce a clinical syndrome of diabetes mellitus and distinctive skin lesions, which can be cured by tumor resection. Hormone-secreting tumors may provide insight into normal gut physiology.
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PMID:Gastrointestinal hormones in clinical disease: recent developments. 21 42

The following significant disturbances of the blood flow were revealed in the liver of 104 patients suffering from diabetes mellitus as a result of rheographic studies: a reduction of the amplitude-frequency index, of the sphygmometric velocity and of its components--the rate of rapid and slow blood filling. The intestinal hormones--secretion and cholecystokinin-pancreosimin improved these indices. The duration of their effect (1.5 U/kg, intravenously) was not less than 20, and not less than 10 min, respectively.
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PMID:[Liver circulation under the effect in intestinal hormones in patients with diabetes mellitus]. 84 67

Digestive enzymatic activities (disaccharidases, alkaline phosphatase, peptide hydrolases) have been determined in the mucosa of 14 patients with chronic pancreatitis. All had an abnormal secretin-pancreozymin test. Four patients had insulin-dependent diabetes mellitus, four a pathological glucose tolerance test. Nine patients had steatorrhoea. Maltase, sucrase, and alkaline phosphatase activity was significantly elevated in patients with exocrine pancreatic insufficiency, whereas those of lactase, trehalase, and peptide hydrolase were normal. Patients with steatorrhoea had higher maltase and sucrase activity than those without steatorrhoea, whereas decreased glucose tolerance had no effect on brush border enzymatic activity. It is suggested thatdecreased exocrine rather than decreased endocrine pancreatic function is responsible for the increase in intestinal disaccharidase and alkaline phosphatase activity, possible by the influence of pacreatic enzymes on the turnover of brush border enzymes from the luminal side of the mucosal membranes or by direct hormonal stimulation though cholecystokinin.
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PMID:Influence of exocrine and endocrine pancreatic function on intestinal brush border enaymatic activities. 109 2

We have developed a sensitive, specific and reproducible radioimmunoassay for cholecystokinin (CCK) with which basal levels of CCK of between 400-800 pg/ml have been measured in normal man, in patients with diabetes and with duodenal ulcer disease, and in normal dogs. After a meal, circulating levels of CCK rose to 1000-1200 pg/ml in human subjects. Release of CCK was more rapid in diabetic and duodenal ulcer patients than in normal subjects, but elevated postprandial levels persisted much longer in normal subjects. Patients with the Zollinger-Ellison syndrome had elevated values of cholecystokinin which rose after a meal. Lack of correlation between elevated basal levels of gastrin and CCK in patients with the Zollinger-Ellison syndrome suggest that the hypercholecystokininemia may be absolute. The disappearance half-time of exogenous CCK was about 21/2 minutes in normal subjects as well as in diabetic and duodenal ulcer patients. Studies in dogs demonstrated no uptake of basal levels of cholecystokinin by the kidney; on infusion of exogenous CCK-33, the kidney extracted 43% of the total CCK presented and 56% of the integrated CCK. We conclude that: 1) circulating basal and postprandial levels of CCK may be measured in a reproducible fashion; 2) postprandial release of CCK is more rapid in diabetic and duodenal ulcer patients than in normal man; 3) the disappearance half-time of exogenous CCK in man and dogs is about 21/2 minutes; 4) the kidney is a major site for uptake of CCK.
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PMID:Cholecystokinin metabolism in man and dogs. 118 May 86

This article explores the mechanisms by which peripheral gastrointestinal hormones produce central nervous system effects on memory and feeding. Cholecystokinin produces its satiety effects and memory-enhancing effects by stimulating ascending vagal fibers. Hyperglycemia has been demonstrated to be a cause of memory dysfunction in persons with diabetes mellitus. A number of other hormones, such as amylin and bombesin, modulate both memory processing and feeding. The causes of the anorexia of aging are briefly reviewed.
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PMID:Effects of peripheral hormones on memory and ingestive behaviors. 143 55

Reviews in brief the studies of the effects of some non-glucose regulators of various origins on pancreatic insulin secretion mediated by endocrine, paracrine, and neurocrine mechanisms, carried out in this laboratory. Model experiments with primary monolayer cultures of isolated islet cells have helped demonstrate a direct insulinotropic effect of STH, TRH, C-terminal tetrapeptide cholecystokinin, opioid peptides and blood plasma of patients with insulin-dependent diabetes mellitus. The findings evidence that the insulinotropic effect of the blood serum of patients with type I diabetes may be associated with both stimulation and suppression of the functional activity of the cultivated islet cells. This latter type of effect influences the basal and glucose-stimulated secretion of insulin. The destructive effect of the plasma of patients with insulin-dependent diabetes on the function of islet cell culture is confirmed by the presence of autoantibodies to islet cell surface antigens in the plasma of 53-55% of the examined patients and by a cytotoxic effect in 45% of cases.
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PMID:[Insulinotropic factors in health and disease]. 148 May 83

The dependence on extracellular Ca2+ for the insulinotropic effect of cholecystokinin-8 (CCK-8) and CCK-8-induced cellular events in isolated rat islets was investigated. CCK-8 stimulated insulin secretion at 8.3 mM glucose in the presence but not in the absence of extracellular Ca2+. In contrast, efflux of 45Ca2+ from 45Ca(2+)-prelabelled islets was stimulated by CCK-8 to the same extent in the presence as in the absence of extracellular Ca2+. This shows that CCK-8 mobilizes intracellularly stored Ca2+. CCK-8 also stimulated 3H-efflux from myo-[2-3H]inositol-prelabelled islets showing that the peptide activates phosphoinositide (PI) hydrolysis. The PI-hydrolysis persisted, but was reduced, in the absence of extracellular Ca2+. This suggests that PI-hydrolysis might underly the liberation of intracellularly stored Ca2+ induced by CCK-8. CCK-8 also stimulated 86Rb(+)-efflux (reflecting K(+)-movements) from 86Rb(+)-prelabelled islets. This effect was clearly reduced, but not absent, in a Ca(2+)-deficient medium, suggesting opening of Ca(2+)-dependent K(+)-channels. Our results show that although CCK-8 mobilizes intracellularly stored Ca2+ and stimulates PI-hydrolysis also in the absence of extracellular Ca2+, the insulinotropic effect of CCK-8 requires the presence of extracellular Ca2+.
Diabetes Res 1991 Mar
PMID:Dependence on extracellular Ca2+ for the effects of cholecystokinin-8 in rat pancreatic islets. 166 46

Gastrointestinal hormones with insulinotropic effects, like cholecystokinin (CCK) and gastric inhibitory polypeptide (GIP) might tentatively be used in the treatment of non-insulin-dependent diabetes mellitus. We therefore examined the effects of intravenous injection of pharmacological dose levels of CCK-8 (100 and 300 pmol/kg), CCK-33 (100 pmol/kg), GIP (100 pmol/kg), and CCK-8 plus GIP (100 pmol/kg of each) on plasma levels of glucose, insulin, somatostatin, glucagon, and pancreatic polypeptide (PP) in healthy human volunteers. The peptides were given under basal conditions or in combination with a mixed meal. CCK-8, CCK-33, and GIP were all found to increase the basal plasma levels of insulin, somatostatin, and PP; the increases were observed already in samples taken at 2 min after the injection. In contrast, the plasma glucagon levels were unaffected by the peptides. CCK-8, CCK-33, and GIP (100 pmol/kg) all potentiated the meal-induced plasma responses of insulin and PP, whereas plasma levels of glucagon after the meal were not affected. Plasma somatostatin levels after the meal were increased by GIP but not affected by CCK-8 or CCK-33. CCK-8 and GIP together (100 pmol/kg for both) increased plasma levels of insulin, PP and somatostatin as much as each of the peptides given alone, both under basal conditions and after the meal intake. Plasma levels of glucagon were not affected by CCK-8 and GIP together. We conclude that in man, both CCK-8, CCK-33, and GIP moderately stimulate basal and meal related insulin release without any synergistic effects and that the peptides do not inhibit the secretion of glucagon.
Diabetes Res Clin Pract 1991 Sep
PMID:Effects of cholecystokinin (CCK)-8, CCK-33, and gastric inhibitory polypeptide (GIP) on basal and meal-stimulated pancreatic hormone secretion in man. 168 22

Both insulin and glucocorticosteroid (GS) deficiency causes a reduction of amylase synthesis and changes in the dose-response curve of cholecystokinin (CCK) stimulated enzyme secretion in rats. Since we found a reduction of plasma insulin in adrenalectomized rats, we now tested the hypothesis that the regulation of amylase synthesis by insulin may be mediated by GS. Three groups of male rats were investigated: controls, streptozotocin induced diabetics, and diabetics treated with GS. Animals were sacrificed 10-14 days after injection of streptozotocin and isolated pancreatic acini prepared by collagenase digestion. Protein synthesis was measured on the translational level by incubation of acini with 35S-methionine followed by lysis of cells and separation of proteins by SDS-PAGE. In addition, protein synthesis was measured on the transcriptional level by isolation of mRNA from pancreatic acini and translation of proteins using the rabbit reticulocyte lysate system. The loss of insulin in diabetic rats was associated with a 70-90% decrease in amylase synthesis and increases of synthesis of various proteases. This was due to a specific decrease in mRNA coding for amylase and increase in mRNA coding for proteases. Furthermore, the known rightward shift of the dose response curves of CCK stimulated amylase secretion was seen in diabetic animals. Treatment of diabetic rats with GS did deteriorate the catabolic status seen in diabetes with increases in mortality as compared to diabetes alone. However, neither the overall pattern of enzyme synthesis seen in diabetic rats nor the alterations in CCK stimulated enzyme secretion were changed by treatment with GS. We conclude that the regulation of amylase synthesis and enzyme secretion by insulin is not mediated via GS.
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PMID:Pancreatic enzyme synthesis and secretion are independently regulated by insulin and glucocorticosteroids. 170 71

Insulin deficiency leads to a decreased ability of cholecystokinin octapeptide (CCK-8) to raise cytosolic free-calcium levels in the pancreatic acinar cell. To elucidate the mechanisms underlying this defect, we studied the effects of CCK-8 on phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis in pancreatic acini prepared from nondiabetic and streptozocin-induced diabetic rats. Analysis by high-pressure liquid chromatography indicated that, in diabetic rat acini, the CCK-8-mediated increase in [3H]inositol 1,4,5-trisphosphate ([3H]IP3) levels was delayed, and the increase in [3H]inositol 1,3,4,5-tetrakisphosphate ([3H]IP4) levels was markedly attenuated compared with nondiabetic rat acini. The expected increase in the mass levels of IP3, measured in a competitive binding assay, was reduced in the diabetic group after incubation with CCK-8, carbachol, and bombesin. Phospholipase C activity was decreased by 30% in diabetic rat acini, whereas the specific activity of PIP2 and the amount of myo-[3H]inositol in the free and trichloroacetic acid-precipitable pools were similar in both groups. The nonhydrolyzable analogue of GTP guanosine-5'-O-(3'-thiotriphosphate) rapidly enhanced IP3 levels in permeabilized acini, and the percent increase above basal was greater in the diabetic group. When added for 5 s or 2 h, insulin did not alter basal or CCK-8-stimulated [3H]IP3 and [3H]IP4 levels in either nondiabetic or diabetic rat acini. However, after a 4-h incubation, insulin increased basal [3H]IP3 and [3H]IP4 levels in diabetic rat acini and potentiated the actions of CCK-8 on both inositol phosphates. Insulinlike growth factor I did not alter [3H]IP3 and [3H]IP4 levels either acutely or after a 4-h incubation. These findings point to a defect in the signal-transduction pathway that is activated by CCK-8 and other calcium-mobilizing agonists in the diabetic rat pancreas and suggest that insulin, acting via its own receptor, exerts long-term regulatory effects on PIP2 hydrolysis in the pancreatic acinar cell.
Diabetes 1991 Oct
PMID:Alteration of cholecystokinin-mediated phosphatidylinositol hydrolysis in pancreatic acini from insulin-deficient rats. Evidence for defective G protein activation. 193 91


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