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

Exocrine pancreatic function was studied in 20 juvenile-onset diabetics, seven maturity-onset diabetics, and five patients with diabetes secondary to chronic pancreatitis. The results were compared with 13 non-diabetic controls. The outputs of bicarbonate, trypsin, and amylase were reduced in the diabetic patients in response to intravenous secretin and CCK-PZ. In the juvenile-onset group, exocrine pancreatic secretory capacity was reduced in 80% of the patients, and the severity of the reduction was related to the duration of the diabetes. The reduction in pancreatic secretory capacity must be taken into consideration when interpreting pancreatic exocrine function in patients with diabetes.
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PMID:Exocrine pancreatic function in juvenile-onset diabetes mellitus. 97 8

The effects of repeated injections of 75 U crude cholecystolinin-pancreozymin (CCK-PZ) at increasing plateau glucose concentrations achieved by glucose infusion were studied in 15 controls, 8 chronic pancreatitics and 8 mild maturity onset diabetics. In control subjects CCK-PZ alone caused minor insulin release but proportinally greater secretion with increasing blood glucose concentrations. Chronic pancreatitis patients who had normal responses to intravenous glucose responded normally to the CCK-PZ but at significantly higher plateau glucose levels. Diabetics had no response to IV glucose boluses of 5 g or 10 g, but with glucose infusions of 250-500 mg/min had almost normal insulin responses to CCK-PZ. The responses to CCK-PZ plus glucose were greater than either stimulus alone, indicating an interaction between these and the beta cell. These studies suggest that the gut homone-receptor in the beta cell is intact in maturity onset diabetes and chronic pancreatitis, whether the glucose receptor is normal or defective. The peptide-responsible in the crude CCK-PZ is not secretin, glucagon or gut glucagon, but may be gastric inhibitory polypeptide (GIP) since pure CCK-PZ has no insuli releasing properties.
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PMID:Insulin responses to crude cholecystokinin-pancreozymin in normal subjects, in patients with chronic pancreatitis and patients with mild maturity onset diabetes. 115 Aug 59

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

The influence of longterm increase in the plasma CCK levels on beta-cell function in rats was studied by using the pancreatico-biliary diversion (PBD) model. An intravenous glucose load (800 mg glucose/kg) was performed three weeks after the PBD operation. Additionally a group of PBD operated animals as well as an unoperated group received the CCK receptor antagonist L364,718 continuously during the three week study period. The proliferation rate of endocrine pancreatic cells was studied by means of 3H-thymidine administration. PBD caused a decrease in basal levels of insulin and glucose and an augmented insulin secretory response after glucose injection. There was no appreciable influence on the glucose elimination rate. When PBD animals were given the CCK receptor antagonist no differences were observed with regard to insulin and glucose compared to PBD animals without antagonist. The CCK-antagonist did not influence the beta-cell function in unoperated animals. Further, the proliferation rate of the endocrine pancreatic cells was not significantly changed in the PBD rats. The results suggest that PBD is accompanied by significant changes in basal and stimulated insulin secretion. These changes are probably not a direct consequence of the increased plasma CCK levels that follows PBD. Moreover, the insulin secretory response to glucose in normal rats was not influenced by longterm administration of the CCK receptor antagonist. Our observations should encourage further studies on the complex entero-insular interactions following pancreaticobiliary diversion.
Diabetes Res 1991 Nov
PMID:Cholecystokinin is not a major determinant for the changes in beta-cell function seen after pancreatico-biliary diversion in rats. 184 24

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

The present study was undertaken to evaluate the changes of gastrointestinal hormones and pancreatic functions after major pancreatectomy in dogs and human. After more than 92% pancreatectomy in dogs, all dogs developed diabetes mellitus (DM). In these dogs, the remnant pancreas showed poor regeneration rate of 24.0% at 6 weeks, decreased sigma IRI in IV-GTT had not been recovered, pancreatic glucagon response was diminished, pancreatic exocrine function had been declined with increased plasma levels of secretin and CCK, and gastric secretion increased in spite of diminished gastrin response. After 74 to 92% pancreatectomy, 17.6% of dogs developed DM. The dogs with DM had poor pancreatic regeneration rate of 22.7% at 12 weeks, hypersecretion of glucagon and decreased gastric secretion with low plasma concentration of gastrin. On the other hand, in dogs without DM, pancreatic regeneration rate showed 42.7% at 12 weeks, insulin release and pancreatic exocrine function had been recovered well, and plasma CCK levels increased without changes of gastric secretion. In the clinical study, gastric secretion, CCK response and pancreatic endocrine and exocrine functions had been maintained better after pylorus preserving pancreaticoduodenectomy than after conventional pancreaticoduodenectomy.
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PMID:[Clinical and experimental studies on pancreatic functions and gastrointestinal hormones after major pancreatectomy]. 194 87

The effects of physiological doses of sulfated cholecystokinin-8 (CCK-8) on insulin secretion were investigated in unrestrained unanesthetized rats. The routes of administration were intravenous or intraportal infusion. Intravenous infusion (0.33-5.0 micrograms CCK-8.kg-1.20 min-1) resulted in a biphasic response pattern consisting of a fast 1st-min rise in plasma insulin concentration and a slower second phase that lasted throughout the infusion. The first phase showed the same amplitude with all amounts of CCK-8 administered in this study, whereas the second phase exhibited dose dependency. Blood glucose levels were lowered during all infusions of CCK-8, although the second phase of insulin release was absent with the lowest dose. These results suggest a strong stimulatory effect of CCK-8 on the pancreatic beta-cells, probably by changing the set point for glucose. The described effects of intravenous administration of CCK-8 cannot be produced when the infusion is given into the portal vein. Only very high concentrations of CCK-8 (15 micrograms.kg-1.20 min-1) produced a small increase in plasma insulin levels, indicating a strong CCK-8-eliminating mechanism in the liver. These results indicate that 1) CCK-8 evokes biphasic insulin release and a concomitant drop in glucose levels, and 2) CCK-8 acting on the beta-cell in vivo is not of intestinal origin but is probably released by the pancreatic vagal branch.
Diabetes 1990 Jun
PMID:Biphasic insulin secretion after intravenous but not after intraportal CCK-8 infusion in rats. 218 62

Central administration of alloxan reduces the hyperphagic, but not the hyperglycemic response to glucoprivation by presumably acting upon brain glucoreceptors or a glucoprivic control mechanism. The present study evaluated whether central alloxan pretreatment respectively altered the dose-dependent suppressant effects upon deprivation (24-hr)-induced feeding of naloxone (0.01-10 mg/kg, IP) and cholecystokinin octapeptide (CCK-8: 1-8 micrograms/kg, IP) in rats. Central alloxan (200 micrograms, ICV) failed to alter body weight, free-feeding and deprivation-induced feeding. Both naloxone and CCK-8 produced significant dose-dependent inhibitions of deprivation-induced feeding in control rats. Central alloxan treatment significantly diminished peak naloxone hypophagia induced by 2.5 and 10 mg/kg doses, and CCK-8 hypophagia induced by the 1 and 4 micrograms/kg doses. Coadministration of 3 M D-glucose, which acts as a cytoprotectant against alloxan-induced diabetes, blocked the attenuating actions of alloxan upon naloxone and CCK-8 hypophagia. These data indicate the effectiveness of central alloxan in restricting the ability of pharmacological agents to either stimulate or inhibit food intake in rats without altering basal intake or body weight maintenance.
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PMID:Inhibition of deprivation-induced feeding by naloxone and cholecystokinin in rats: effects of central alloxan. 233 18

A disturbed intraduodenal milieu and pancreatic scarring in advanced chronic pancreatitis (CP) may lead to changes of gut and pancreatic hormones. In the present study, the gastroduodenal mucosal content of several regulatory peptides was determined in 8 patients with severe calcific CP and 8 healthy volunteers. In addition, hormone release into the bloodstream was estimated after intraduodenal acid/glucose stimulation in the control subjects and 8 CP patients each with or without secondary diabetes mellitus (DM), and in 8 patients with juvenile DM, so that disturbed gut hormone release could be attributed either to CP or DM. While VIP release into the circulation was similar in all participants, mucosal levels of VIP and substance P were significantly elevated in the duodenal bulb and descending duodenum of CP patients. The somatostatin content of gastroduodenal mucosa in CP was at least as high as in normals. Gastrin was significantly more abundant only in the duodenal bulb of CP patients, while plasma gastrin was normal. Duodenal CCK concentrations tended to be elevated in the duodenal bulb, but not significantly. The release of secretin seemed to be higher in type-1 diabetics than in CP patients. The mucosal pattern of GIP was nearly identical in CP patients and controls. Compatible with this finding, the GIP release did not show any peculiarities in CP with or without DM or in DM. Basal and stimulated plasma levels of motilin were abnormally high in CP. Pancreatic polypeptide plasma levels were normal in DM, but significantly reduced in CP, especially in CP with DM. Fasting PP and stimulated pancreatic enzyme outputs were linearly related.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chronic pancreatitis and diabetes mellitus: plasma and gastroduodenal mucosal profiles of regulatory peptides (gastrin, motilin, secretin, cholecystokinin, gastric inhibitory polypeptide, somatostatin, VIP, substance P, pancreatic polypeptide, glucagon, enteroglucagon, neurotensin). 246 85

The effect of cholecystokinin (CCK-33) and its fragments, C-terminal octapeptide (CCK-8) and C-terminal tetrapeptide (CCK-4), on arterial blood pressure and on the function of the isolated rat heart was studied in three groups of animals: normal (C group), rats with streptozotocin-induced diabetes of one month's duration (DM group) and with diabetes treated with insulin (DMI group). CCK-33 (5.0, 10.0 and 20.0 U/kg iv) raised dose-dependently systolic and diastolic arterial blood pressure but did not change the heart rate in the group of normal rats. CCK-33 administered in doses of 1.0, 2.0, 5.0 U/0.1 ml) increased the amplitude of the isolated heart contraction and reduced heart rate but had no effect on coronary outflow in this group. In the diabetic rats, CCK-33 in dose 20.0 U/kg iv reduced the arterial blood pressure and had no effect on heart rate in vivo. CCK-33 increased the cardiac contraction amplitude and lowered heart rate of the isolated heart from the diabetic rats. In the group of insulin-treated diabetic rats, CCK-33 did not change the blood pressure, increased the heart rate in vivo. This peptide increased the cardiac contraction amplitude, no lowering of the heart rate of the isolated heart was noted. CCK-8 and CCK-4 had no effect on arterial blood pressure and the function of the isolated heart in any of the groups of animals studied. The results indicate that shortening of CCK-33 to CCK-8 and CCK-4 eliminates the circulatory effect of this peptide and that in diabetes CCK-33 produces circulatory effects opposite to those observed in normal animals. Insulin partially normalizes the action of CCK-33 on the circulation in diabetes.
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PMID:Effects of cholecystokinin (CCK-33) and its fragments, C-terminal octapeptide (CCK-8) and C-terminal tetrapeptide (CCK-4), on the circulatory system of diabetic rats. 248 4


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