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

Contractility of the gall bladder (by ultrasound criteria) and pancreatic enzyme excretion were considerably decreased in patients with diabetes mellitus of noninsulin dependent type in the presence of atrophic duodenitis, confirmed by endoscopy and histology, as compared to diabetic patients without duodenitis or with non-atrophic duodenitis. The data obtained were discussed with relation to a decrease in the excretion in atrophic duodenitis of cholecystokinin-pancreozymin (the main physiological stimulator of motility of the gall bladder and pancreatic enzyme excretion). It turned out that contractility of the gall bladder in patients with diabetic neuropathy was much less than that in diabetic patients without neuropathy provided all other conditions were the same. All the results obtained permitted better understanding of the essence, mechanisms and clinical meaning of gastroenterological disorders in patients with diabetes mellitus.
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PMID:[Significance of duodenitis and disorders of gall bladder motility in patients with diabetes mellitus]. 194 3

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.
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PMID:Pancreatic polypeptide and other pancreatic hormones in spontaneously diabetic BB/W rats. 198 Jul 35

A bioassay using dispersed pancreatic acini was used to measure fasting plasma cholecystokinin (CCK) concentrations in 105 patients with various kinds of gastrointestinal diseases, 17 patients with diabetes mellitus, and 6 healthy volunteers. High plasma CCK bioactivities were observed in patients with obstructive jaundice, choledocolithiasis, and primary biliary cirrhosis. Twenty-three samples with high CCK bioactivities were assayed by the same bioassay after the addition of a specific CCK antagonist and by a CCK radioimmunoassay in order to determine whether the high CCK-like bioactivity was due to circulating CCK or other factors. High CCK bioactivities were partially inhibited by the specific CCK antagonist, CR-1409, but the activities were not totally abolished. The residual bioactivities (not inhibited by CR-1409) correlated with plasma bile acid concentrations. The inhibitable CCK bioactivities correlated with plasma CCK levels obtained by radioimmunoassay. Although the bioassay using dispersed pancreatic acini has several advantages for measuring plasma CCK, this method overestimates CCK bioactivities in patients with high plasma bile acid concentrations.
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PMID:Bile acids in human plasma interfere with cholecystokinin bioassay using dispersed pancreatic acini. 199 67

The cholecystokinin-tetrapeptide (CCK4) analogs Trp-Pro-Asp-Phe-NH2 (3) and Trp-Pro-Asp-Phe-(4'-NO2)-NH2 (4) were found to be nearly equipotent to cholecystokinin-octapeptide (CCK8) in potentiating glucose-induced insulin secretion from islets of Langerhans isolated from rat pancreas. This stimulatory action was found to be dose-dependent and, in the case of 4, to exhibit a biphasic dose-response curve; i.e., at concentrations greater than 1.0 nM, the stimulating effect of 4 is reversed. These results suggest that conformational restriction of CCK4 and/or modification of the phenylalanine residue could produce more potent analogs capable of stimulating insulin release. Such compounds could have potential therapeutic utility in the treatment of non-insulin-dependent diabetes mellitus (NIDDM).
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PMID:Stimulation of insulin secretion from pancreatic islets by the cholecystokinin-tetrapeptide analogs Trp-Pro-Asp-Phe-NH2 and Trp-Pro-Asp-Phe(4'-NO2)-NH2. 213 65

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

Mechanisms by which various classes of extracellular signals regulate insulin secretion are discussed regarding their cellular and molecular actions. Under physiological circumstances, the small postprandial changes in plasma glucose concentrations (approximately 4.4-6.6 mM) primarily serve as a conditioned modifier of insulin secretion and dramatically alter the responsiveness of islets to a combination of neurohormonal agonists. These agonists have two functions. Cholecystokinin (CCK) and acetylcholine activate the hydrolysis of polyphosphoinositides, and gastric inhibitory polypeptide (GIP) and glucagonlike peptide 1 activate adenylate cyclase. These two functional classes of neurohumoral agonists act synergistically to enhance insulin secretion when plasma glucose is greater than 6.0 mM but not when it is less than or equal to 4 mM. On the other hand, an increase in plasma glucose concentration to 8-10 mM induces an increase in insulin secretory rate in the absence of any of the neurohormonal agonists. Remarkably, high glucose leads to an increase in the same intracellular signals, as does a combination of acetylcholine and GIP. On the basis of these data, a model of how insulin secretion is regulated under physiological circumstances is proposed. This model emphasizes that the regulation of insulin secretion occurs in three stages: cephalic, early enteric, and later enteric. In this view, the crucial event occurring during the first two phases is the agonist-induced, translocation of protein kinase C (PKC) to the plasma membrane under conditions in which an increase in Ca2+ influx does not occur. PKC is now in a cellular location and a Ca2(+)-sensitive conformation such that an increase in Ca2+ influx rate occurring during the third phase leads to its immediate activation and an enhanced rate of insulin secretion. Furthermore, under physiological circumstances, an optimal insulin secretory response is dependent on a correct temporal pattern of signals arising from neural and enteric sources. If this pattern is deranged, an abnormal pattern of insulin secretion is observed. An important new insight is provided by the observation that agonists (e.g., CCK or acetylcholine) that act to stimulate the hydrolysis of phosphatidylinositides, when acting for a short period (10-20 min), induce an enhanced responsiveness of islets to glucose, i.e., proemial sensitization. However, when acting unopposed for several hours, these agonists will induce a time-dependent suppression of responsiveness to glucose and other agonists. The latter observation implies that optimal insulin secretion is dependent on periodic rather than a continuous exposure to the correct pattern of extracellular signals.(ABSTRACT TRUNCATED AT 400 WORDS)
Diabetes Care 1990 Jun
PMID:Physiology and pathophysiology of insulin secretion. 219 49

Patients affected by diabetes mellitus are reported to have an increased incidence of gallbladder abnormalities. The pathophysiologic mechanisms for this phenomenon are unclear. In the present study ultrasonography was used to determine gallbladder emptying in response to a meal or separate cephalic or hormonal stimulation in 21 diabetic patients and 10 healthy subjects. Gallbladder emptying and refilling after a meal were similar in diabetic patients and healthy subjects. When diabetics were divided according to the presence or absence of cardiac autonomic neuropathy (AN), a significant reduction of gallbladder emptying in response to cephalic stimulation was found in diabetics with AN (P less than 0.01 in comparison with diabetics without AN or healthy subjects). A dose-response curve of gallbladder emptying in response cerulein, a cholecystokinin analog, at concentrations of 0.25, 1, and 4 micrograms/kg/min was evaluated. No differences of gallbladder emptying were found in the three groups of subjects, indicating that gallbladder sensitivity to hormonal stimulation is not changed in diabetic patients with or without AN. Diabetic patients with AN have a significant reduction of gastric acid output and pancreatic polypeptide (PP) secretion in response to cephalic stimulation (P less than 0.05 in comparison with diabetic patients without AN or healthy subjects). Cerulein-induced PP secretion was similar in all three groups of subjects (P greater than 0.05). This study indicates that in diabetic patients with AN, gallbladder emptying as well as gastric acid and PP secretions induced by neural stimulation are markedly reduced in comparison to diabetics without AN.
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PMID:Neurohumoral control of gallbladder motility in healthy subjects and diabetic patients with or without autonomic neuropathy. 220 70

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

Recent studies indicate that insulin directly regulates the acinar pancreas. Morphologic and hemodynamic studies indicate the presence of a portal system that conveys islet blood to acinar cells. Studies both in humans with diabetes mellitus and in animals given beta cell toxins indicate that insulin is necessary for normal acinar cell function. Studies in the perfused rat pancreas indicate that endogenous insulin potentiates zymogen release. Isolated rat and mouse acini have insulin receptors, and in these cells, after binding to its receptors, insulin regulates a number of functions including: sugar transport, protein synthesis, and the number of cholecystokinin receptors. These in vivo and in vitro studies suggest, therefore, that there is an insulin-pancreatic acinar axis that plays a major role in pancreatic function.
Diabetes 1985 Oct
PMID:The insulin-pancreatic acinar axis. 241 19

Both adrenalectomy and chemically induced diabetes mellitus cause a marked decrease of pancreatic amylase synthesis in rats. Diabetes is further associated with alterations of cholecystokinin (CCK)-stimulated enzyme secretion. Using isolated pancreatic acini prepared from adrenalectomized male rats, we investigated the effects of adrenalectomy on pancreatic enzyme secretion. CCK8-stimulated amylase secretion showed a typical biphasic dose-response curve in acini from both adrenalectomized and sham-operated animals with similar basal secretions, similar sensitivities to various CCK8 concentrations, but a statistically significant elevation of maximal amylase secretion after adrenalectomy. Receptor-binding studies with 125I-BH-CCK8 revealed an increase of binding to the high-affinity part of the CCK receptor in adrenalectomized rats. While carbachol-stimulated secretion showed no changes in maximal secretion rates, it did show a decrease in sensitivity in adrenalectomized animals with a statistically significant shift to the right of the dose-response curves. Competitive inhibition curves with 3H-N-methylscopolamine and carbachol as the competitive receptor agonist showed no differences in receptor binding between controls and adrenalectomized rats. We propose that complex alterations in hormone/neurotransmitter-stimulated pancreatic enzyme secretion are found in glucocorticoid depletion, explainable via a postreceptor defect in carbachol-stimulated secretion. The functional and binding data with regard to CCK are more difficult to explain.
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PMID:Influence of adrenalectomy on pancreatic enzyme secretion. 246 11


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