UMLS:C0011849 - FACTA Search

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

To test the hypothesis that diabetic hyperphagia results from insulin deficiency in the brain, diabetic rats (streptozotocin-induced) were given an intracerebroventricular (ICV) infusion of saline or insulin (at a dose that did not affect plasma glucose levels) for 6 days. Food and water intake were significantly increased in diabetic rats, but only food intake was affected by ICV insulin. Diabetic hyperphagia was reduced 58% by ICV insulin compared with ICV saline (P < 0.05) and was accompanied by a 69% increase in diabetes-induced weight loss (P < 0.05). To evaluate whether central nervous system (CNS) insulin deficiency affects expression of neuropeptides involved in food intake, in situ hybridization was done for neuropeptide Y (NPY), which stimulates feeding, in the hypothalamic arcuate nucleus and for cholecystokinin (CCK) and corticotropin-releasing hormone (CRH), which inhibit feeding, in the hypothalamic paraventricular nucleus. In diabetic rats, NPY mRNA hybridization increased 280% (P < 0.05), an effect reduced 40% by ICV insulin (P < 0.05). CCK mRNA hybridization increased 50% in diabetic rats (P < 0.05), a response reduced slightly by ICV insulin (P < 0.05), whereas CRH mRNA hybridization decreased 33% in diabetic rats (P < 0.05) and was unchanged by ICV insulin. The results demonstrate that CNS infusion of insulin to diabetic rats reduces both hyperphagia and overexpression of hypothalamic NPY mRNA. This observation supports the hypothesis that a deficiency of insulin in the brain is an important cause of diabetic hyperphagia and that increased hypothalamic NPY gene expression contributes to this phenomenon.
Diabetes 1995 Feb
PMID:Effect of intracerebroventricular insulin infusion on diabetic hyperphagia and hypothalamic neuropeptide gene expression. 785 32

Glucagon-like peptide-1 (GLP-1) is promptly released from endocrine cells of the distal part of the gut after oral ingestion of a meal. To test the possibility that hormones produced by the proximal small intestine or transmitters of the enteric nervous system may be involved in the early phase of meal-induced GLP-1 secretion, various intestinal regulatory peptides and neurotransmitters of the gut were administered intraarterially in the isolated vascularly perfused rat colon preparation. The release of GLP-1 in the portal effluent was measured by a specific RIA. Intraarterial infusion of glucose-dependent insulinotropic peptide (GIP) over the concentration range 0.25-1 nM evoked a dose-dependent release of GLP-1, with a maximal response of 350% of the basal value. Tetrodotoxin did not modify the GIP-induced release of GLP-1. Secretin or cholecystokinin did not stimulate the secretion of GLP-1. Bombesin (10(-9)-10(-7) M) provoked a dose-dependent release of GLP-1, consisting of an early peak, followed by a sustained response. Calcitonin gene-related peptide (5 x 10(-8) M) induced a dramatic rise of GLP-1 immunoreactivity in the portal effluent (peak at 800% of the basal value 10 min after the start of infusion). Similarly, the beta-adrenergic agonist isoproterenol at concentrations of 10(-7) and 10(-6) M provoked a pronounced release of GLP-1 (peak at 500% of the basal value with 10(-6) M isoproterenol). Finally, the muscarinic cholinergic agonist bethanechol at a concentration of 10(-4) M evoked a gradual increase in GLP-1 immunoreactivity, which reached a maximal value (900% over basal) at the end of the 30-min infusion period. The lowest concentration of bethanechol used in the present study (10(-5) M) did not increase portal GLP-1 immunoreactivity over the basal value. Tetrodotoxin did not modify the bethanechol-, isoproterenol-, calcitonin gene-related peptide-, or bombesin-induced GLP-1 release. In conclusion, the present study conducted with the isolated vascularly perfused rat colon shows that there are interactions between the two most potent incretins, GIP and GLP-1, probably through an enteroendocrine pathway. Additionally, several transmitters of the gut are potent stimulants of GLP-1 release and, therefore, represent potential tools in the treatment of the noninsulin-dependent diabetes mellitus.
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PMID:Regulation of glucagon-like peptide-1-(7-36) amide secretion by intestinal neurotransmitters and hormones in the isolated vascularly perfused rat colon. 798 23

Patients with diabetes mellitus are at increased risk of developing gallstones. This has been attributed, among other factors, to alterations in gallbladder motility in the presence of autonomic neuropathy. Since high blood glucose concentrations impair gastric emptying in diabetic patients, we have investigated the effect of acute hyperglycaemia on gallbladder motility. Seven Type 1 (insulin-dependent) diabetic patients were studied twice during euglycaemia (blood glucose 5 mmol/l) and hyperglycaemia (blood glucose 15 mmol/l) using a clamp technique. In addition, seven healthy volunteers were studied during euglycaemia and hyperglycaemia. Gallbladder volumes, measured with ultrasonography, were studied before and during infusion of step-wise increasing doses of cholecystokinin-33, 0.25, 0.5 and 1.0 Ivy Dog Unit.kg-1.h-1, each dose for 30 min. Mean basal gallbladder volumes were not significantly different in the four experiments. Administration of cholecystokinin resulted in significant (p < 0.05) dose-dependent reductions in gallbladder volume in all experiments. During euglycaemia the gallbladder contraction in diabetic patients was not significantly different from the control subjects. During hyperglycaemia the gallbladder contraction in the diabetic patients was significantly (p < 0.05) reduced compared to euglycaemia only during infusion of 0.25 Ivy Dog Unit.kg-1.h-1 of cholecystokinin (19 +/- 6% vs 33 +/- 6%). Compared to euglycaemia, during hyperglycaemia the gallbladder contraction in the control subjects was significantly (p < 0.05) reduced during infusion of 0.25, 0.5 and 1.0 Ivy Dog Unit.kg-1.h-1 of cholecystokinin (14 +/- 4% vs 31 +/- 3%; 42 +/- 6% vs 65 +/- 5%; 74 +/- 4% vs 90 +/- 3%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of hyperglycaemia on gallbladder motility in type 1 (insulin-dependent) diabetes mellitus. 815 Feb 34

In the absence of any other exogenously added fuel, monomethylsuccinate, the methyl ester of succinic acid, at 10-20 mM stimulates insulin release in a biphasic pattern. In quantitative terms, first-phase release evoked by 20 mM MMSucc was comparable to that observed with 20 mM glucose but second-phase release was only 20% of the glucose-induced response. Secretion to both MMSucc and glucose was virtually abolished by the calcium channel antagonist nitrendipine (0.5 microM). In islets that had phosphoinositide pools labeled with [3H]inositol for 2 h, subsequent stimulation with 20 mM MMSucc results in dramatic and sustained increases in [3H]inositol efflux rates. Inositol phosphate levels are also increased. In contrast to secretion, the increase in phosphoinositide hydrolysis caused by MMSucc was largely resistant to nitrendipine, whereas significant reductions in glucose-induced phosphoinositide hydrolysis were observed in the presence of the calcium channel antagonist. MMSucc (2.75-10 mM) substitutes for glucose in that MMSucc supported the insulinotropic effects of the sulfonylurea tolbutamide (200 microM) and the gut hormone cholecystokinin (200 nM). A prior 15-min exposure to 20 mM MMSucc also sensitized islets to the stimulatory effects of 7.5 mM glucose. Finally, a 2-h exposure to 20 mM MMSucc desensitized the islet, in terms of both phosphoinositide hydrolysis and insulin secretion, to a subsequent exposure to 10 mM glucose. Thus, appropriate concentrations of MMSucc can cause qualitatively many of the effects induced by glucose.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1993 Jun
PMID:Comparative effects of monomethylsuccinate and glucose on insulin secretion from perifused rat islets. 838 41

Chronic feeding of normal rats with camostate, a synthetic trypsin inhibitor, stimulates the growth of the pancreas chiefly by increasing cholecystokinin release. We examined the effects of camostate on the growth and the endocrine function of the pancreas in streptozotocin-induced diabetic rats. The pancreatic weight of the diabetic rats given camostate (200 mg/kg/day) by oral gavage for 14 days was significantly elevated by 120% over that of diabetic rats not given camostate, and was comparable to that in the nondiabetic rats given camostate. The total pancreatic contents of DNA, RNA, and protein in diabetic rats given camostate were also significantly higher than those in diabetic rats not given camostate, and did not differ from those observed in nondiabetic rats given camostate. The pancreatic growth seen in diabetic rats treated with camostate was associated with moderate hyperplasia and pronounced hypertrophy. By contrast, treatment with camostate did not improve hyperglycemia, hypoinsulinemia, or low pancreatic content of insulin seen in diabetic rats. These findings demonstrate a marked growth of the pancreas in diabetic rats stimulated by camostate, and suggest that camostate-induced pancreatic growth is not affected by the reduced level of the endogenous insulin. The present study also indicates that camostate has no beneficial effects on the function of residual B cells, failing to improve diabetes.
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PMID:Chronic effects of camostate on growth and endocrine function of the pancreas in streptozotocin-induced diabetic rats. 841 77

In a previous study we demonstrated that patients with recently diagnosed non-insulin-dependent diabetes mellitus (NIDDM) had significantly increased gastric emptying rates of glucose solutions compared with those of nondiabetic sex- and age-matched controls. This finding of rapid gastric emptying contrasts with the delayed gastric emptying often exhibited as a late manifestation of diabetes mellitus that is attributed to autonomic neuropathy. The purpose of this study was to determine, in seven of the patients previously studied, whether (1) an intravenous infusion of cholecystokinin-8 (CCK-8) would delay the gastric emptying of a liquid glucose meal and, if so, (2) whether the delay in gastric emptying would result in reduced postprandial blood glucose concentrations due to prolongation of the absorption of the glucose in the liquid meal. Each patient underwent two separate gastric emptying studies, one during a saline infusion and one during a CCK-8 infusion. Blood samples were obtained at 15-min intervals for measurement of glucose, insulin, CCK-8, and gastric inhibitory polypeptide (GIP) concentrations. The average gastric half-emptying time was 41 min with the saline infusion and 94 min with the CCK-8 infusion (P = 0.0042). The average glucose concentration over the 2-hr period following glucose ingestion was 17.1 mmol/liter with the saline infusion and 14.0 mmol/liter with the CCK-8 infusion (P = 0.0073). The average glucose excursion value over the 2-hr period was reduced from 5.6 mmol/liter to 3.7 mmol/liter with the CCK-8 infusion (P = 0.0550).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduced postprandial blood glucose levels in recently diagnosed non-insulin-dependent diabetics secondary to pharmacologically induced delayed gastric emptying. 842 Jul 60

The plasma cholecystokinin (CCK) response to a test meal was studied in 16 control subjects and 15 patients with noninsulin-dependent diabetes mellitus (NIDDM). Basal CCK levels were approximately 1 pmol in both groups. However, after the test meal, plasma CCK levels were 2-fold greater in the controls when compared to the diabetics. In controls, CCK levels maximally increased by 5.6 +/- 0.8 pmol (mean +/- SEM) 10 min after feeding, whereas in the NIDDM patients this value was 1.9 +/- 0.6 pmol (P < 0.001). After the test meal, the normal subjects showed no postprandial rise in blood glucose, whereas the diabetic patient showed a rise of 2.6 +/- 0.7 mmol. To determine whether the decreased CCK levels may have been related to the postprandial hyperglycemia, 7 diabetic subjects were infused with CCK. With this CCK infusion, postprandial glucose levels did not rise. These data suggest, therefore: 1) a role for cholecystokinin in regulating postprandial hyperglycemia in man, 2) abnormalities in CCK secretion occur in NIDDM and may contribute to the hyperglycemia seen in this disease.
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PMID:Reduced postprandial cholecystokinin (CCK) secretion in patients with noninsulin-dependent diabetes mellitus: evidence for a role for CCK in regulating postprandial hyperglycemia. 843 95

The role of glucose in the regulation of plasma cholecystokinin (CCK) level was investigated in healthy control subjects and patients with non-insulin-dependent diabetes mellitus (NIDDM). Plasma CCK concentration was determined by a specific and sensitive bioassay and by a highly sensitive and reliable double-antibody radioimmunoassay using OAL-656 as an antiserum. In control subjects, ingestion of Trelan G-75 (1,200 mOsm/L,225 mL), which is equivalent to 75 g glucose as metabolic products, caused a rapid and significant increase in plasma CCK bioactivity from 1.3 +/- 0.2 to a peak of 5.8 +/- 0.6 pmol/L and immunoreactive CCK concentration from 1.2 +/- 0.1 to 4.6 +/- 0.6 pmol/L. Ingestion of 75 g glucose in 225 mL water (33.3% solution) increased plasma CCK bioactivity to a similar degree to that observed following Trelan G-75 (peak response, 4.5 +/- 0.4 pmol/L). The same volume of 0.9% NaCl solution or water failed to increase plasma CCK concentration. A smaller dose of glucose (50 b/150 mL water) increased plasma CCK concentration, although the peak level (3.0 +/- 0.5 pmol/L) was less than that observed following 75 g glucose. In patients with NIDDM, Trelan G-75 ingestion increased CCK concentration, but the peak level was lower, albeit insignificantly, than that of normal subjects. When the maximal increment of plasma CCK above the basal value was compared between control and NIDDM subjects, the differences were statistically significant (NIDDM, 3.6 +/- 0.1 pmol/L; control, 5.0 +/- 0.4; P < .01). However, integrated CCK responses to Trelan G-75 in NIDDM (165.8 +/- 15.5 pmol/120 min) were not significantly different from those in control subjects (189.8 +/- 15.9 pmol/120 min). Peak CCK bioactivity occurred within 10 to 30 minutes of ingestion, preceding the increase in glucose and insulin. These results suggest a possible effect of CCK on insulin release in humans, and that the CCK secretory response to glucose in well-controlled diabetic patients is not significantly altered.
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PMID:Oral glucose ingestion stimulates cholecystokinin release in normal subjects and patients with non-insulin-dependent diabetes mellitus. 859 89

The effects of streptozotocin-induced diabetes on pituitary neuropeptides were studied. Substance P, dynorphin and beta-endorphin in both pituitary lobes and cholecystokinin and somatostatin in the neurointermediate lobe (NIL) were measured 4 weeks after streptozotocin treatment in adult male rats. There were significant decreases of substance P levels in both the anterior lobe (AL) and NIL, and of cholecystokinin, dynorphin and beta-endorphin in the NIL, whereas the dynorphin content in the AL increased, when values were expressed on a per-lobe basis. On a per-milligram-protein basis, however, only beta-endorphin in the NIL showed a significant decrease, while AL beta-endorphin and dynorphin were increased. Correlated with these changes were a drastic decrease in the serum insulin level and a marked increase in serum glucose and corticosterone levels. All these changes were reversible with insulin treatment. It is suggested that the decrease in NIL contents of neuropeptides demonstrated (except for beta-endorphin) might be due to mechanisms other than a change in synthesis.
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PMID:Pituitary contents of beta-endorphin, dynorphin, substance P, cholecystokinin and somatostatin in rats with streptozotocin-induced diabetes. 873 22

This work extends a recent observation that Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which have been established as an animal model of non-insulin-dependent diabetes mellitus, show no expression of the cholecystokinin (CCK)-A receptor gene in the pancreas. The CCK-A receptor is known to be involved in regulating pancreatic exocrine function and growth. We examined the growth of the pancreas in terms of wet weight, enzyme compositions, and protein and DNA contents at 5-6 and 24-25 weeks of age in OLETF rats and control (Long-Evans Tokushima; LETO) rats. The pancreatic wet weight increased significantly with age in both OLETF and LETO rats but was significantly lower in OLETF rats than in LETO rats. The total DNA contents in the whole pancreas (cell numbers) were comparable for both strains and increased significantly with age. However, the ratio of protein content to DNA content (the cell size) significantly increased with age in LETO rats, with no increase in OLETF rats. The changes in chymotrypsin, amylase, and insulin with respect to age were in the same direction in both strains: a decrease or no change in total and/or cellular contents of chymotrypsin and insulin and increases in amylase. These results suggest that the CCK-A receptor plays some role in the increase in cell size associated with normal growth of the pancreas from 5 to 25 weeks of age (after weaning).
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PMID:Role of cholecystokinin (CCK)-A receptor for pancreatic growth after weaning: a study in a new rat model without gene expression of the CCK-A receptor. 874 Apr 1

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