Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three-dimensional magnetic resonance cholangiopancreatography is currently the most exciting new imaging technique for chronic pancreatitis. Endoscopy-assisted duodenal intubation during the secretin-cholecystokinin test reduces intubation time in difficult cases. The NBT-para-amino benzoic acid test has been refined to enhance its discriminant power. The cholesteryl-[C13]octanoate breath test and the faecal elastase test are newer highly sensitive and specific tubeless tests. Pain in chronic pancreatitis continues to be a vexing therapeutic issue. Enzyme treatment continues despite criticism. Neurotensin is the new suspected mediator of the feedback mechanism, which is downregulated by enzyme therapy. Steroid ganglion block is an exciting therapeutic tool for pain relief. Endoscopic pancreatic sphincterotomy, Dormia basketing and pancreatic stenting in conjunction with extracorporeal shock wave lithotripsy should be performed early in chronic pancreatitis to prevent parenchymal atrophy with ensuing exocrine and endocrine pancreatic dysfunction. The modified Puestow's procedure preserves endocrine and exocrine pancreatic functions besides relieving pain. Closed loop insulin infusion allows superior management of pancreatic diabetes following near total pancreatectomy. The standardised incidence rate of pancreatic cancer is 16.5 in patients with alcoholic chronic pancreatitis and 100 for tropical chronic pancreatitis. Aggressive treatment protocols combining neo-adjuvant chemoradiation and intra-operative radiation with surgery are being used to improve the prognosis in this dismal complication of chronic pancreatitis.
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PMID:Chronic pancreatitis: diagnosis and treatment. 875 8

We investigated intracellular Ca2+ regulation in pancreatic acinar cells from rats with diabetes induced by a single injection of streptozotocin (80 mg/kg). Experiments were performed 2 days and 7 days after the injection of streptozotocin. The density of muscarinic receptors, measured by [3H]N-methyl scopolamine binding, was unchanged in 2-day-diabetic rats, but was significantly increased in 7-day-diabetic rats. The percentage of high affinity receptors (RH) and low affinity receptors (RL) determined from the competitive curves with [3H]N-methyl scopolamine and carbachol was not change in 2-day-diabetic rats compared to controls, whereas 7-day-diabetic rats showed a decrease in %RH and an increase in %RL. The carbachol-evoked initial peak of intracellular Ca2+ concentration ([Ca2+]i) was increased in 2-day-diabetic rats and decreased in 7-day-diabetic rats, compared to controls. In the carbachol-induced sustained phase in [Ca2+]i, the response in 7-day-diabetic rats was significantly decreased; however, there was no difference between controls and 2-day-diabetic rats. Carbachol (100 microM)-induced [3H]inositol 1,3,4-trisphosphate generation was significantly lower in diabetic rats than in the controls. The addition of inositol 1,4,5-trisphosphate (1,4,5-IP3) significantly increased 45Ca2+ release from saponin-permeabilized cells in 2-day-diabetic rats, but did not do so in 7-day-diabetic rats. Ca2+ refilling into the intracellular stores, determined by second cholecystokinin-8 (10 nM) stimulation after 10 microM carbachol stimulation, was increased in 2-day-diabetic rats and decreased in 7-day-diabetic rats. These observations indicate that the alterations in intracellular Ca2+ regulation accompanied by changes in transmembrane signaling occur in the earlier stage of the diabetic state. The findings also suggest that the increase in the carbachol-evoked [Ca2+]i peak in 2-day-diabetic rats is related predominantly to the higher sensitivity of 1,4,5-IP3-sensitive Ca2+ stores and the increase in the capacity of Ca2+ refilling in these animals, whereas the reduction in the [Ca2+]i peak in 7-day-diabetic rats appears to be related to the essential decrease in receptor-mediated 1,4,5-IP3 generation and the decrease in Ca2+ refilling capacity.
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PMID:Altered intracellular Ca2+ regulation in pancreatic acinar cells from acute streptozotocin-induced diabetic rats. 884 30

There is clear evidence of a positive correlation between carbohydrate absorption, plasma concentration of glucose, and the rate of gastric emptying. This suggests that clinical manipulation of gastric emptying rates may have therapeutic potential in glycaemic control. Cholecystokinin (CCK-8) has been shown to delay gastric emptying in individuals with Type 2 diabetes, but its potential as a therapy is limited by the need to administer it intravenously. The preferred routes of administration would be intramuscular injections, an intranasal spray or the use of orally ingested CCK analogues. Alternatively, the oral administration of an agent that enhances endogenous release of CCK could represent an important approach to the treatment of Type 2 diabetes. Agents such as POT II may have a therapeutic indication in patients with recently diagnosed Type 2 diabetes.
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PMID:Decelerating gastric emptying: therapeutic possibilities in type 2 diabetes. 889 71

The effect of cholecystokinin (CCK-33) and its fragments, CCK-8 and CCK-4, on arterial blood pressure and the function of isolated rat heart and catecholamine levels in plasma and from isolated heart tissue in diabetes mellitus were studied. The results indicated that, in diabetes, cardiovascular effects of CCK-33 and CCK-8 are diminished or abolished. Diabetes can change the response of the alpha- and beta-adrenergic system to CCK-33 and CCK-8 and the contents of catecholamines in heart tissue.
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PMID:Cholecystokinin (CCK) and C-terminal fragments of CCK: effects of CCK-33, CCK-8 and CCK-4 in the cardiovascular system of diabetic rats. 891 64

Clinical as well as experimental studies in insulinopenic diabetes mellitus have demonstrated abnormal pancreatic exocrine responses to cholecystokinin (CCK). In the present study, we examined pancreatic exocrine and endocrine function in the recently developed genetically diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats and compared them with those in the control Long-Evans Tokushima Otsuka (LETO) rats of the same age. Stepwise increasing doses of CCK octapeptide (CCK-8; 0.027-7.0 nmol.kg-1.h-1) evoked a characteristic biphasic dose-response curve for pancreatic juice and protein output in the LETO rats, whereas the OLETF rats were totally insensitive to CCK-8 stimulation. However, the responsiveness and the sensitivity to both carbamylcholine and secretin were similar in the two groups. Intraduodenal infusion of casein (500 mg/h) failed to stimulate pancreatic exocrine secretion in the OLETF rats despite a greater CCK response than in the LETO rats (peak response: 8.43 +/- 0.97 vs 5.12 +/- 0.30 pmol/l in LETO, P < 0.01). Intravenous infusion of CCK-8 (4.4 nmol.kg-1.20 min-1) caused a significant increase in serum insulin concentrations and a concomitant decrease in glucose levels in the LETO rats but not in the OLETF rats. On the other hand, an intravenous bolus injection of 1.1 mmol/kg glucose caused a greater insulin release in the OLETF rats than in the LETO rats. In contrast, gastric acid secretion in the OLETF rats was significantly high in basal and in response to intravenous infusion of CCK-8 compared with that in the LETO rats. Four subcutaneous injections of 20 micrograms/kg caerulein at hourly intervals over 3 h induced acute pancreatitis in the LETO rats but did not elicit any significant increase in serum amylase or lipase activities and pancreatic wet weight or histological evidence of acute pancreatitis in the OLETF rats. These results indicate that the exocrine and endocrine pancreas of the recently developed genetically diabetic OLETF rats are totally and specifically insensitive to exogenous and endogenous CCK stimulation, whereas parietal cells in these rats are sensitive to CCK stimulation.
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PMID:Defect in pancreatic exocrine and endocrine response to CCK in genetically diabetic OLETF rats. 892 5

In this paper a new immunological model of anorexia and bulimia nervosa will be presented in which the inflammatory cytokines are conceived as the fundamental regulators of body metabolism. This conception differs from the conventional view in which the inflammatory cytokines are perceived primarily as peptide molecules utilized by the immune system to control infection, inflammation and tissue or neuronal damage. Given that the inflammatory cytokines are also fundamental regulators of body metabolism, when they become dysregulated they create physiological chaos which results in the development of a number of autoimmune, metabolic and psychiatric disorders. In this proposed immunological model of anorexia and bulimia nervosa, elevated tumor necrosis factor-alpha features as the primary cause of these conditions. Pathophysiological parallels are drawn between anorexia nervosa and cancer cachexia in terms of the causal role the cytokines, neuropeptides and neurotransmitters play in the manifestation of shared symptoms. These shared symptoms include elevated tumour necrosis factor-alpha, down-regulated interleukin-2 and interleukin-4 and depletion of lean body mass. Furthermore, the following neuropeptides are dysregulated in both anorexia nervosa and cancer cachexia: vasoactive intestinal peptide, cholecystokinin, corticotropin-releasing factor, neuropeptide Y, peptide YY and beta-endorphin. In addition, in anorexia and bulimia nervosa, secretion of the neurotransmitter serotonin is inhibited while norepinephrine is enhanced. It will be argued that the causal interplay between the cytokines, neuropeptides and neurotransmitters initiates a cascade of biochemical events which may result in either anorexia or bulimia nervosa, or cancer cachexia. The extent to which these inflammatory cytokines, neuropeptides and neurotransmitters are causally efficacious in the pathogenesis of other autoimmune disorders, such as diabetes mellitus and rheumatoid arthritis, will also be addressed.
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PMID:The role of tumor necrosis factor-alpha in the pathogenesis of anorexia and bulimia nervosa, cancer cachexia and obesity. 896 Dec 38

Patients with early non-insulin-dependent diabetes mellitus (NIDDM) empty glucose solutions from their stomachs more rapidly than non-diabetic control subjects, and this exacerbates postprandial hyperglycaemia. To determine if accelerated gastric emptying occurred in a rat model of NIDDM and influenced postprandial hyperglycaemia, gastric emptying of glucose was measured, and the effect of slowing the gastric emptying rate on postprandial hyperglycaemia was observed. We tested eight male obese Zucker diabetic rats and eight age-matched lean Zucker controls at 10-13 weeks of age to measure gastric emptying of glucose (by gamma scintigraphy). Rats fasted overnight were gavaged with 30% glucose at 1 ml/100 g body weight. Separately, six Zucker diabetic rats and six lean controls were tested for sensitivity to the inhibitory effects of cholecystokinin and secretin on gastric emptying. The diabetic rats emptied glucose significantly faster than controls (t1/2 = 37.3 +/- 1.5 vs 58.8 +/- 2.3 min in controls), and aging exaggerated this differential. Camostat, a stimulant of cholecystokinin and secretin release, added to the glucose meal significantly slowed gastric emptying (t1/2 = 123 +/- 23 and 166 +/- 19 min, diabetic vs lean, respectively), and significantly reduced postprandial hyperglycaemia in diabetic rats. Compared to Zucker lean controls, Zucker diabetic rats were as sensitive (cholecystokinin) or more sensitive (secretin) to gastrointestinal hormones that inhibit gastric emptying. The results demonstrate accelerated gastric emptying in a rat model of NIDDM, consistant with similar observations in humans with early NIDDM. These results also support the proposal that interventions to slow gastric emptying improve glucose control in this disease.
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PMID:Accelerated gastric emptying of glucose in Zucker type 2 diabetic rats: role in postprandial hyperglycaemia. 904 72

The interaction of C-terminal cholecystokinin octapeptide (CCK-8) with beta-adrenoceptors agonist (isoprenaline-ISO) and antagonist (propranolol) and their influence on arterial blood pressure and function of isolated heart in rats with streptozotocin-induced diabetes mellitus (DM) was studied. After blockade of beta-adrenoceptors with propranolol, the hypertensive effect of CCK-8 was observed in the control group but not in DM-group, whereas CCK-8 had no effect on arterial blood pressure in the both studied groups. Stimulation of beta-adrenoceptors with ISO exerted the hypotensive effect of CCK-8 similar as after administration of the amine alone in the control and diabetic rats. CCK-8 increased the cardiac contraction amplitude and had no effect on heart rate and coronary outflow in control hearts. The positive inotropic effect of the peptide was abolished in DM-group. After blockade of beta-adrenoceptors, CCK-8 decreased all studied parameters of isolated hearts, the effect was similar as after infusion of propranolol alone. In DM group, after blockade of beta-adrenoceptors CCK-8 evoked decrease in the cardiac contraction amplitude (as during infusion of propranolol) and heart rate (the effect was greater than that after beta-adrenoceptors antagonist). CCK-8 administrated with ISO increased amplitude, heart rate and decreased coronary outflow of isolated control heart as after administration of ISO alone: in DM-group only the positive inotropic effect was observed. DM modified the effect of CCK-8 in circulatory system of rats. CCK-8 evoked bradycardia independent of stimulation or blockade of beta-adrenoceptors, mainly in DM.
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PMID:Interaction of cholecystokinin (CCK-8) with agonist and antagonist of beta-adrenergic receptors in circulatory system of diabetic rats. 911 65

Psammomys obesus fed a high-calorie diet develops a NIDDM-like syndrome. The use of reverse-phase high-performance liquid chromatography (HPLC) to study Psammomys insulin biosynthesis and release revealed a very delayed elution time for the Psammomys insulin peak appearing near the position of human proinsulin. This unusual peak was initially thought to represent partially processed insulin on the basis of its molecular size and susceptibility to trimming by carboxypeptidase B (CpB). However, the findings of an active carboxypeptidase E (CpE) enzyme and the normal amidated forms of gastrin and cholecystokinin octapeptide (CCK-8) in Psammomys tissues were inconsistent with CpE-related aberrant processing of insulin. Moreover, amino acid sequencing of the delayed peak of Psammomys insulin revealed fully processed insulin with amino acid sequence as predicted by the cDNA. The unique presence of a B-30 phenylalanine residue, resulting in an increased hydrophobicity of the insulin molecule, probably underlies the marked delay in elution time on HPLC. The unusual structure of Psammomys insulin does not appear to contribute to the proinsulinemia observed in diabetic Psammomys since the HPLC-purified molecule did not inhibit PC1 and PC2 convertase activities in an in vitro assay.
Diabetes 1997 Jun
PMID:Characterization of the unusual insulin of Psammomys obesus, a rodent with nutrition-induced NIDDM-like syndrome. 916 65

The effects of nutrient and neurotransmitter stimuli on insulin release, loss of phosphoinositides (PI), and production of inositol phosphates (InsP) were investigated in islets from neonatally streptozotocin-injected (nSTZ) rats. In islets from nSTZ rats, insulin secretory responses to 16.7 mM D-glucose and 10.0 mM D-glyceraldehyde were reduced compared with controls. Contents in phosphatidylinositol 4-monophosphate [PtdIns(4)P] and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2], but not in phosphatidylinositol, were diminished. Glucose effects on breakdown of PtdIns(4)P and PtdIns(4,5)P2 and on total InsP accumulation were both reduced. D-Glucose was unable to increase the levels of both inositol trisphosphate isomers, Ins(1,3,4)P3 and Ins(1,4,5)P3. Glyceraldehyde also failed to promote InsP formation. By contrast, the ability of 1.0 mM carbachol or 300 nM cholecystokinin to stimulate insulin secretion and InsP generation was still observed. Thus a disturbed coupling between nutrient recognition and activation of phospholipase C, possibly together with a shortage of available polyphosphoinositides, could be responsible for the altered islet PI turnover in the nSTZ rats. It is proposed that such defects may contribute to the impairment of glucose-stimulated insulin secretion in this model of non-insulin-dependent diabetes mellitus.
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PMID:Impaired phosphoinositide metabolism in glucose-incompetent islets of neonatally streptozotocin-diabetic rats. 917 70


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