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)

To determine whether insulin is essential for the augmented hepatic glucose uptake observed in the presence of intraportal glucose delivery, SRIF was used to induce acute insulin deficiency in 5 conscious dogs, and glucose was infused into the portal vein or a peripheral vein in two sequential, randomized periods. Insulin and C-peptide levels were below the limits of detection after SRIF infusion, and the load of glucose presented to the liver was approximately doubled and equivalent during the portal and peripheral periods. Net hepatic glucose output was 2.9 +/- 0.9 and 2.1 +/- 1.1 mumol.kg-1.min-1 during portal and peripheral glucose delivery, respectively. In an additional set of protocols, pancreatectomized dogs were used to investigate the effects of prolonged insulin deficiency (n = 5) and acute insulin replacement (n = 4) on the hepatic response to intraportal glucose delivery. In the prolonged insulin deficiency protocol, SRIF was used to lower glucagon and thereby reduce circulating glucose levels, and glucose was infused into the portal or peripheral circulations in two sequential, randomized periods. As with acute insulin deficiency, net hepatic glucose output was still evident and similar (3.6 +/- 1.1 and 4.2 +/- 1.3 mumol.kg-1.min-1) during portal and peripheral glucose delivery, respectively. When the pancreatectomized dogs were restudied using a similar protocol, but one in which insulin was replaced (4X-basal), and the glucose load to the liver was matched to that which occurred in the prolonged insulin deficiency protocol, net hepatic glucose uptake was 23.6 +/- 6.1 mumol.kg-1.min-1 during portal glucose delivery but only 10.3 +/- 3.5 mumol.kg-1.min-1 during peripheral glucose delivery. These results suggest that the induction of net hepatic glucose uptake and the augmented hepatic response to intraportal glucose delivery require the presence of insulin.
Diabetes 1992 Oct
PMID:Insulin is required for the liver to respond to intraportal glucose delivery in the conscious dog. 139 97

The effect of continuous infusions of somatostatin (SRIF) on growth hormone (GH) secretion induced by GH-releasing hormone (GHRH) bolus was compared in a dose-response manner between diabetic subjects in poor glycemic control and nondiabetic subjects to address the hypothesis that altered pituitary responsiveness to SRIF contributes to the hypersecretion of GH in diabetes mellitus in humans. Studies were conducted with a modification of the euglycemic clamp technique to minimize fluctuations in glucose and insulin. Suppression of GHRH-induced GH secretion was demonstrable in diabetic subjects only at a SRIF dose 15-fold higher than that at which suppression could be detected in nondiabetic subjects. The calculated 50% inhibitory dose (ID50) in diabetic subjects was 4-fold higher than that in nondiabetic subjects (P = 0.03). In diabetic subjects after 2 wk of intensive insulin management, the change in the dose-response curve persisted despite significant decrements in glycosylated hemoglobin and increments in plasma insulinlike growth factor I. The increment in plasma SRIF predicted at the SRIF ID50 from concentrations measured during the SRIF infusions in nondiabetic subjects would result in hypophyseal portal SRIF concentrations in the physiological range reported in recent animal studies, whereas those for the ID50 in diabetic subjects would be approximately 1.5-2.5 times the upper limit of that range. These studies indicate that pituitary resistance to the action of SRIF occurs in men with insulin-dependent (type I) diabetes at physiological concentrations of the hormone and is therefore highly likely to contribute to the hypersecretion of GH in diabetes.
Diabetes 1991 Oct
PMID:Resistance of growth hormone secretion to somatostatin in men with type I diabetes mellitus. 168 93

Diabetes mellitus in the rat is associated with loss of pulsatile GH secretion. An interplay between hypothalamic GH-releasing factor (GRF) and inhibitory factor [somatostatin (SRIF)] secretion is thought to account for episodic pituitary GH release. An increase in SRIF tone/action or a decrease in GRF release/response in diabetic rats could account for the suppressed GH levels. Pituitaries from streptozotocin-diabetic rats contained less GH than controls (15.9 +/- 2.5 vs. 29.5 +/- 4.6 micrograms/mg; P less than 0.05) despite normal somatotrope representation, as demonstrated using immunofluorescence studies. Basal GH secretion from monolayer culture of dispersed anterior pituitary (AP) cells from diabetic rats was proportionately decreased (150 +/- 10 vs. 103 +/- 10 ng/10(5) cells; P less than 0.005). GRF (10(-11)-10(-8) M)-induced release of GH from AP cells was decreased in diabetic rats (maximum response to 10(-8) M GRF, 401 +/- 60 vs. 618 +/- 41 ng/10(5) cells; P less than 0.01); however, sensitivity to GRF was unchanged (EC50, 79 +/- 41 vs. 128 +/- 67 pM). By contrast, SRIF (10(-7)-10(-10)-induced inhibition of GRF (10(-8) M)-mediated GH release was impaired in AP cells of diabetic rats compared to that in controls (IC50, 112 +/- 33 vs. 55 +/- 31 pM; P less than 0.05) associated with a decrease in AP plasma membrane SRIF receptor concentration (63.4 +/- 15.6 vs. 160.3 +/- 13.7 fmol/mg protein; P less than 0.05), with no change in affinity. These findings are consistent with chronic exposure to increased hypothalamic SRIF influence. GH synthesis has been shown to be independent of SRIF regulation; however, insulin-like growth factor-I and GRF inhibit and stimulate GH synthesis, respectively. In diabetic rats insulin-like growth factor-I levels were decreased, appropriate to low GH status, in serum (290 +/- 66 vs. 1662 +/- 92 ng/ml; P less than 0.001) and hypothalamus (6.8 +/- 1.0 vs. 13.0 +/- 0.4 pg/mg wet wt; P less than 0.001) and, thus, did not seem to account for the low AP GH content. Hypothalamic GRF content in diabetic rats (1.11 +/- 0.10 ng/hypothalamus) did not differ from that in controls (1.16 +/- 0.17 ng/hypothalamus). GRF mRNA levels, however, were reduced by 80% in diabetic rats compared to controls. Taken together these data support a combined role for decreased hypothalamic GRF and increased SRIF in mediating alterations of GH synthesis and secretion in streptozotocin-induced diabetes.
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PMID:Altered pituitary growth hormone (GH) regulation in streptozotocin-diabetic rats: a combined defect of hypothalamic somatostatin and GH-releasing factor. 196 64

The in vivo labeling of somatostatin-14, somatostatin-28, arginine vasopressin, and oxytocin was studied in rat hypothalamus after third ventricular administration of [35S]cysteine to streptozotocin-diabetic and normal rats. Immunoreactive somatostatin levels in hypothalamus were unaffected by diabetes, as was the incorporation of [35S]cysteine into hypothalamic somatostatin-14 and somatostatin-28. In contrast, immunoreactive vasopressin levels in hypothalamus and posterior pituitary (and oxytocin levels in posterior pituitary) were below normal in diabetic rats. Moreover, [35S]cysteine incorporation into hypothalamic vasopressin and oxytocin (probably mainly in the paraventricular nucleus because of its proximity to the third ventricular site of label injection) was significantly above normal. The increments in vasopressin and oxytocin labeling were reversed by insulin administration. In vivo cysteine specific activity and the labeling of acid-precipitable protein did not differ between normal and diabetic animals; effects of diabetes on vasopressin and oxytocin labeling were therefore not caused by simple differences in cysteine specific activity. These results suggest that diabetes 1) does not influence the production of somatostatin peptides in hypothalamus but 2) stimulates the synthesis of vasopressin and oxytocin. For vasopressin at least, the increase in synthesis may be a compensatory response to the known increase in its secretion that occurs in uncontrolled diabetes.
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PMID:In vivo somatostatin, vasopressin, and oxytocin synthesis in diabetic rat hypothalamus. 197 Jul 6

Free fatty acids are known to inhibit carbohydrate disposal and oxidation. This action may play an important role in the pathophysiology of insulin resistance and non-insulin-dependent diabetes mellitus. To investigate whether amino acids (AAs) have similar actions, we determined the effects of an intravenously infused mixture of 15 AAs on carbohydrate disposal during euglycemic-hyperinsulinemic clamps associated with either basal or high glucagon concentrations in healthy male volunteers. Plasma glucose concentration was clamped at approximately 4.7 mM (coefficient of variation 4.7%). Insulin infusion (7.18 pmol.kg-1.min-1) raised serum insulin concentrations from 36-50 pM to between 300 and 600 pM. AA infusions (0.5 g.kg-1.h-1.4 h) raised plasma alpha-amino N2 concentrations about five- to six-fold. Infusion of AAs, somatostatin (somatotropin release inhibitory factor, SRIF), and high-glucagon replacement (3.0 ng.kg-1.min-1) reduced the rate of exogenous glucose infusion needed to maintain euglycemia from 51.1 +/- 7.2 mumol.kg-1.min-1 (saline + SRIF + high glucagon) to 28.3 +/- 11.1 mumol.kg-1.min-1 and stimulated endogenous glucose production (from 0 to approximately 17 mumol.kg-1.min-1). Thus, glucose disposal (exogenous infusion plus endogenous production of glucose) remained essentially unchanged. During infusion of AAs + SRIF + basal glucagon replacement (0.25 ng.kg-1.min-1), endogenous glucose production remained completely suppressed, and the rates of exogenous glucose infusion did not change (compared with saline + SRIF + basal glucagon replacement). The data showed that 1) hyperaminoacidemia associated with hyperglucagonemia stimulated endogenous glucose production despite hyperinsulinemia, and 2) intravenous infusion of a mixture of 15 AAs had no inhibitory effect on insulin-stimulated total-body glucose disposal.
Diabetes 1990 Sep
PMID:Effects of amino acids on glucose disposal. 197 39

Recent evidence suggests that somatostatin-28 (SRIF-28), cleaved from prosomatostatin by cells of the upper intestine, acts as a nutrient-stimulated inhibitor of insulin secretion in healthy men. A role for SRIF-28 in the pathophysiology of diabetes has not been previously explored, although several groups have measured circulating somatostatinlike immunoreactivity (SLI) in diabetic subjects. To investigate the possible mediation of abnormal insulin secretion in diabetes by SRIF-28, plasma levels were measured in 10 non-insulin-dependent diabetic men and 9 age- and weight-matched control subjects. Concentrations of SRIF-14 and SLI were also obtained. Subjects were admitted for study after an overnight fast, blood was collected before and at 30-min intervals for 4 h after a fat meal, and plasma samples were analyzed for SRIF-28 and SRIF-14 by specific methods. Basal glucose levels in the diabetic men were significantly higher than in control subjects (10.2 +/- 1 vs. 5.8 +/- 0.2 mM), but insulin levels were similar (79 +/- 14.2 vs. 93.3 +/- 14.2 pM). The diabetic men had significantly lower basal SRIF-28 levels than the control subjects (11.4 +/- 0.6 vs. 14.6 +/- 1.0 pM, P = 0.017). After fat intake, SRIF-28 levels throughout the 4 h of study were indistinguishable in the two groups (270 vs. 292% of basal). Basal SRIF-14 and SLI levels were not significantly different in the two groups, and SRIF-14 and SLI concentrations rose similarly after the meal. There were no correlations between basal SRIF-28 and glucose or insulin levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1990 Oct
PMID:Fasting and postprandial concentrations of somatostatin-28 and somatostatin-14 in type II diabetes in men. 197 58

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

We have attempted to define the nature of insulin secretory defect(s) in aged animals. In these studies, pancreatic islets were isolated from 2- and 18-mo-old Fischer 344 rats. Margination of secretion vesicles during exocytosis was assessed by measuring the recruitment of somatostatin (SRIF) receptors to the surface membrane. Section vesicle lysis was studied by measuring insulin release into the incubation media. Submaximal and maximal glucose-induced insulin secretion was significantly greater in islets isolated from younger rats (P less than 0.01). SRIF receptor recruitment was stimulated by glucose in both younger and older Fischer 344 rats. However, an increase in SRIF receptor recruitment was reduced in islets isolated from older animals (from 2.14 +/- 0.4 to 4.6 +/- 0.4 fmol/10 islets) (P less than 0.01) as compared with islets from younger animals (from 2.6 +/- 0.2 to 6.2 +/- 0.4 fmol/10 islets). When secretion vesicle lysis was inhibited by the presence of sodium isethionate in the incubation media, glucose (300 mg/dl) failed to stimulate secretion vesicle margination to the plasma membrane. In contrast, glyburide (0.6 micrograms/ml) continued to stimulate directly secretion vesicle margination in islets from aged animals (from 2.1 +/- 0.3 to 6.0 +/- 0.3 fmol/10 islets). We conclude that glucose-induced margination of secretion vesicles at the plasma membrane is impaired by the aging process. This impairment results in lower submaximal and maximal insulin secretory response to glucose. The fact that glyburide is capable of stimulating secretion vesicle margination suggests that glucose signal recognition and/or stimulus-secretion coupling may be the locus of impairment in the process of insulin secretion in older animals.
Diabetes 1985 Nov
PMID:The nature of insulin secretory defect in aging rats. 241 20

We previously reported that sulfonylurea treatment reduces insulin (IRI), glucagon (IRG) and somatostatin (SRIF) release following metabolic stimuli from the isolated perfused pancreas of normal rats and that a reduction in IRI, IRG and SRIF pancreatic content was also observed. The present work was undertaken to investigate the effects of long-term glibenclamide treatment on the gastrointestinal content of gut hormones in normal rats. Moreover, the effects of sulfonylurea treatment on IRI, IRG, and SRIF pancreatic content were also analyzed and compared to the peripheral hormone plasma levels. Two groups of male Sprague-Dawley rats received glibenclamide (1 mg/kg/day per os; n = 14) or placebo (distilled water; n = 10) for 5 months, respectively. Tissue contents of IRI, IRG and SRIF in acid-ethanol extracts of pancreas and of gastric inhibitory peptide (GIP), vasoactive intestinal polypeptide (VIP), entero-glucagon (gut-GLI) and SRIF in acid-ethanol extracts of intestine were determined. Blood glucose and plasma pancreatic hormone levels were also measured. Glibenclamide treatment lowered the levels of IRI, IRG and SRIF in the pancreatic tissue; in the same way gut-GLI, SRIF and VIP intestinal concentrations were significantly reduced, whereas no significant inhibition was detected in intestinal GIP content. Blood glucose levels and IRI and SRIF plasma concentrations were similar in the two groups. IRG plasma levels were reduced in the sulfonylurea group. These findings might suggest that sulfonylurea suppresses hormone biosynthesis in a non-specific manner.
Diabetes Res Clin Pract 1989 Feb 15
PMID:Effects of long-term glibenclamide administration on gastrointestinal and pancreatic hormones in normal fasting rats. 249 27

After a 0100-0300 h nadir, the insulin requirements to maintain blood glucose at 90-110 mg/dl increase substantially in the prebreakfast (0600-0800 h) period in some insulin-dependent diabetic patients (IDDMs). Early insulin-like and delayed insulin-antagonistic effects of physiologic early morning increases in growth hormone (hGH) secretion may account for this variability of overnight insulin requirements. To assess the role of hGH, we studied five IDDMs using a closed-loop insulin infusion device (Biostator, GCIIS). Either saline (C) or somatostatin plus glucagon (SRIF + G) was infused during separate overnight (2400-0800 h) study periods. An infusion of hGH from 2400 to 0130 h was added to SRIF + G infusion during an additional study period (SRIF + G + hGH). In comparison to 0100-0300 h, mean insulin infusion rates required to maintain blood glucose values between 105 and 120 mg/dl during the prebreakfast period increased by 66 +/- 25% during C, and 42 +/- 12% during SRIF + G when serum growth hormone was suppressed to less than or equal to 0.75 ng/ml. During SRIF + G + hGH, the mean prebreakfast insulin infusion rate increased by 42 +/- 11% with a mean peak hGH level of 14.7 +/- 5.4 ng/ml at 0130 h. Mean plasma free insulin levels remained constant during the night despite the significantly higher insulin infusion rates between 0600 and 0800 h. During SRIF + G, insulin requirements remained constant overnight before 0600 h, whereas during both C and SRIF + G + hGH conditions, a nadir was noted between 0100 and 0300 h.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1985 Feb
PMID:Influence of growth hormone on overnight insulin requirements in insulin-dependent diabetes. 285 43


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