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

Isolated adipose tissue cells were prepared from subcutaneous samples obtained from nine morbidly obese subjects weighing from 187 to 306% of ideal body weight. The responsiveness of these adipocytes to a number of test substances was determined by measuring cellular cyclic AMP concentration at one-half hour and glycerol release at four hours. Theophylline (10(-3) M) and epinephrine (10(-5) M) stimulated lipolysis; theophylline stimulated an increase in cyclic AMP, while epinephrine failed to prompt a significant change in the nucleotide. Neither the alpha blocker, phentolamine (10(-5) M), nor the beta blocker, propranolol (3 X 10(-5) M), affected lipolysis or cyclic AMP; when these agents were incubated in combination with epinephrine, changes occurred indicative of the presence of both alpha and beta adrenergic receptor sites. Insulin significantly reduced both basal and stimulated lipolysis but failed to affect cyclic AMP. With minor exceptions, adipocytes from hyperobese subjects behaved similarly to cells from unselected donors; at the concentration used, there was no evidence of resistance to insulin.
Diabetes 1977 Jul
PMID:In-vitro observations on isolated adipose tissue cells from hyperobese subjects. 19 9

The active role played by beta-cell microfilamentous structures in the dynamics of insulin secretion was investigated by examining the influence of cytochalasin B upon various parameters of hormonal release by the isolated perfused rat pancreas. The view that the cytochalasin-induced changes in insulin release are due to a primary biophysical effect on microfilaments, rather than to an unrelated biochemical alteration of the beta-cell glucose-sensor device, was strengthened by the following observations: (1) the onset and disappearance of the cytochalasin B-induced facilitating action upon insulin release followed a time-course parallel to that characterizing the ultrastructural changes provoked by the drug in the distribution of beta-cell microfilamentous material; and (2) cytochalasin B facilitated leucine-induced insulin release in the presence of a very low glucose concentration. The mold metabolite was also found to transform transient secretory responses into biphasic ones and to prevent the reduction that normally affects the early response to insulinotropic agents when the pancreas is stimulated a few minutes after a prior and short exposure to glucose. The release of insulin evoked by either glucose or gliclazide was abolished in the absence of extracellular calcium, whether in the presence or absence of cytochalasin B. Theophylline and cytochalasin B exerted a synergistic effect upon glucose-induced insulin release. These data support the concept that calcium-dependent contractile events involving cytochalasin B-sensitive microfilamentous structures provide the motive force for both the intracellular translocation and exocytotic release of beta granules.
Diabetes 1975 Oct
PMID:Dynamics of insulin release and microtubular-microfilamentous system. VII. Do microfilaments provide the motive force for the translocation and extrusion of beta granules? 110 Apr 58

Nonketotic, genetically diabetic Cinese hamsters show subnormal pancreatic insulin release and impaired suppression of glucagon in response to glucose. To study the pancreatic effects of other agents, dynamic insulin and glucagon release was measured from the in vitro perfused pancreases of normal and diabetic Chinese hamsters in response to various combinations of arginine (20mM), glucose (100 or 150 mg. per 100 ml.), and theophylline (10 mM). Theophylline alone caused identical insulin and glucagon release in diabetics and normals. Glucose, alone and in the presence of theophylline, caused subnormal insulin release and less suppression of glucagon release in the diabectics than in the normals. Arginine, in the presence of glucose and theophylline, caused excessive glucagon release but nearly normal insulin release in the diabetics. Arginine, in the absence of glucose or theophylline, caused excessive glucagon release in the diabetics and undetectable insulin release in either diabetics or normals. Pancreatic content after perfusion did not correlate with release during perfusion. Infusion of arginine alone markedly decreased the amount of extractable pancreatic insulin and glucagon. These results indicate that the pancreatic alpha cell of the diabetic Chinese hamster responds excessively to arginine, as is seen in the human diabetic. This defect is not related to acute insulin release or the presence of glucose. Further, these results confirm that the diabetic Chinese hamster's alpha and beta cells respond normally to theophylline, but are relatively insensitive to glucose.
Diabetes 1975 Mar
PMID:Responses to arginine of the perfused pancreas of the genetically diabetic Chinese hamster. 111 50

The pancreas secretes insulin in an oscillatory fashion, but the precise site of the pacemaker for pulsatile insulin secretion has not been identified. These studies were designed to determine whether islets also secrete insulin in a pulsatile fashion if they are isolated from their pancreatic milieu. Isolated rat islets (80-100) were perifused 8 h in culture medium after overnight incubation, and samples were collected at 3.3-min intervals. Insulin secretion was evaluated for pulsatility with the Clifton Cycle Detection Program. Perifusion of islets was associated with a spontaneous, persistent, and regular pulsatility of insulin secretion, which was observed in all conditions tested. Perifusion with medium containing 5.5 mM glucose (n = 11) demonstrated oscillations with a mean periodicity of 17.6 +/- 1.1 min and a mean amplitude of 4.8 +/- 0.4 microU/ml when overall mean insulin concentration was 16.7 +/- 2.4 microU/ml. When the glucose concentration was 16.7 mM (n = 9), overall mean insulin concentration was 54.4 +/- 2.6 microU/ml, with increases in periodicity (22.0 +/- 1.3 min) and amplitude (10.7 +/- 0.5 microU/ml). All measurements were significantly different from those observed during perifusion with 5.5 mM glucose (P less than 0.02-0.001). Theophylline (1 mM) also enhanced the overall mean insulin concentration and amplitude (69.4 +/- 10.4 and 14.2 +/- 1.2 microU/ml, respectively) compared with control studies without theophylline (16.7 +/- 5.3 and 4.3 +/- 0.5 microU/ml) (P less than 0.01). The period of the cycle was also increased from 17.5 +/- 1.1 to 26.4 +/- 6.3 min, but this was not significantly different from the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1990 Jan
PMID:Pulsatile insulin secretion in isolated rat islets. 221 53

Chronic hyperglycemia has been shown to induce a decrease in beta cell sensitivity to a subsequent glucose challenge. Calcium is a necessary cofactor in the insulin secretory process and glucose elevates cytoplasmic levels. This study was designed to study whether chronic exposure to different extracellular calcium and glucose concentrations would affect the islets' subsequent response to regulatory stimuli. Islets were isolated and cultured in TC 199 plus 10% beta calf serum, glucose (5.5 or 27.5 mM) and calcium (0.5, 2.5 or 4.0 mM) for 48 h. Following culture, the islets were harvested and incubated a second time in the presence of glucose and/or arginine, theophylline, and trifluoperazine (TFP). Some islets were used for insulin content, protein synthesis studies and/or CO2 production from labelled glucose. Islets cultured in a normal glucose environment with low or normal calcium concentration maintained the capacity to respond to a subsequent glucose or arginine challenge. However, islets cultured in a high glucose or high calcium medium failed to respond to a second glucose or arginine stimulus. Theophylline stimulated insulin secretion from both glucose-sensitive and non-sensitive islets, while trifluoperazine inhibited glucose-stimulated insulin secretion in previously sensitive islets and increased insulin secretion in previously non-sensitive islets. The different culture conditions did not alter insulin content, protein synthesis or glucose conversion to labelled CO2. We conclude that chronic exposure to high glucose decreases beta cell responsiveness to glucose and amino acids. Increased extracellular calcium augmented this response. However, the beta cell remained sensitive to theophylline-induced insulin secretion, while TFP paradoxically increased insulin secretion in the glucose-insensitive beta cells. Protein synthesis and glucose oxidation were not affected by culture conditions. Thus we suggest that the glucose-induced desensitization of the beta cells may be due to alterations in the calcium-dependent release mechanism.
Diabetes Res Clin Pract 1989 Sep 18
PMID:Beta cell desensitization to glucose induced by hyperglycemia is augmented by increased calcium. 269 Dec 17

Hereditary insulin-deficient diabetes mellitus occurs in certain sublines of nonobese Chinese hamsters. Several characteristics of this syndrome are similar to those seen in insulin-deficient human diabetics. Therefore, to characterize pancreatic islet function, dynamic insulin and glucagon release from normal and nonketotic diabetic hamster pancreases in response to glucose (300 mg/100 ml) and theophylline (10 mM), infused singly and together, was studied in vitro.20-min glucose infusions of normal hamster pancreases caused biphasic insulin release, consisting of a rapid first peak and a gradually rising second phase, similar to that reported for man in vivo. Both phases were significantly reduced in the diabetic pancreases. Theophylline alone stimulated similar nonphasic insulin release in both the normal and the diabetic pancreases. Glucose and theophylline together caused greater insulin release than either stimulant alone in both normals and diabetics; however, the diabetic response was still subnormal. Glucose suppressed glucagon release from normal pancreases; suppression was significantly impaired in diabetics. Theophylline stimulated nonphasic glucagon release in both the normals and diabetics. Glucose partially suppressed the theophylline-stimulated release in both groups.Insulin/glucagon molar ratios of the diabetics were consistently subnormal, although individual hormone levels often overlapped into the normal range. IN SUMMARY, THE PANCREASES OF GENETICALLY DIABETIC CHINESE HAMSTERS PERFUSED IN VITRO SHOWED: (a) decreased first and second phase insulin release in response to glucose-containing stimuli-only partially ameliorated by theophylline-, and (b) impaired suppression of glucagon in response to glucose, resulting in (c) a decreased insulin/glucagon molar ratio. These data support the suggestion that both alpha and beta cells of diabetic pancreases may be insensitive to glucose.
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PMID:Abnormal secretion of insulin and glucagon by the in vitro perfused pancreas of the genetically diabetic Chinese hamster. 483 Feb 28

Substitution of extracellular Cl- by impermeant isethionate (5 mM residual Cl-) caused a monophasic inhibition of glucose-stimulated insulin release, accompanied by an initial transient increase and a secondary lasting decrease in 86Rb+ efflux from perifused islets. Cl- reintroduction restored insulin release with an overshoot above control values and successively produced a small decrease and a large increase in efflux. Theophylline potentiated the insulinotropic effect of glucose more markedly at low Cl- than at normal Cl-, but did not restore a normal rate of 86Rb+ efflux. Lowering the concentration of Cl- did not alter the effect of glucose, tolbutamide, or arginine on 86Rb+ efflux, but simply shifted the efflux rates to lower values. The first phase of glucose-stimulated insulin release was not modified, but the second phase was inhibited. The insulinotropic effect of tolbutamide was augmented at low Cl- and that of arginine (at 7 mM glucose) was not affected. In incubated islets, the stimulation of insulin release by glyceraldehyde was barely inhibited when Cl- was substituted by isethionate and the marked decrease of the effect of glucose could be prevented by glutamine. In a glucose-free, low Cl- medium, the insulinotropic effect of leucine, arginine, and lysine was inhibited; this inhibition was reversed by glutamine, but not by theophylline. Lowering the concentration of Cl- had no effect on 45Ca2+ influx or efflux in the absence of glucose, did not alter the increase in influx and efflux during the first 5 min of glucose stimulation, but impaired both influx and efflux during the second phase. Leucine-induced 45Ca2+ uptake was inhibited at low Cl- and this inhibition was prevented by glutamine. In conclusion, islet cells possess a Cl- -activated modality of K efflux, which does not seem to play a role in the stimulus-secretion coupling. Since Cl- substitution by an impermeant anion does not inhibit the stimulation of insulin release by all agents, the role of Cl- ions does not appear to be restricted to a chemiosmotic mechanism of exocytosis. No single mechanism explains the multiple changes in B-cell function resulting from the decrease in Cl- concentration, but it is proposed that some of them could result from modifications of intracellular pH.
Diabetes 1983 May
PMID:Chloride modulation of insulin release, 86Rb+ efflux, and 45Ca2+ fluxes in rat islets stimulated by various secretagogues. 634 Nov 24

Non-insulin-dependent diabetes ( NIDD ) was obtained in adult rats following a neonatal streptozotocin injection. Rats with NIDD exhibited a chronic low-insulin response to glucose in vivo, slightly elevated basal plasma glucose values (less than 2 g/l) and low pancreatic insulin stores (50% of the controls). Glucagon secretion was studied in this model, in vivo and in vitro using the isolated perfused pancreas technique. Normal basal plasma glucagon levels were observed in the fed state and were in accordance with normal basal glucagon release in vitro. The pancreatic glucagon stores were normal in the diabetics. In experiments with the perfused pancreas, the increased glucose concentration suppressed glucagon release as readily in the diabetics as in the controls. Moreover 5.5 mM glucose suppressed glucagon release stimulated by 19 mM arginine to the same extent in both groups. These data indicate that the suppression of A cell function by glucose is normal in rats with NIDD . Theophylline and isoproterenol also produced normal glucagon release in diabetics. By contrast, the glucagon secretion in response to arginine was lower in the diabetics. This was observed either in vivo (arginine infusion) or in vitro in the presence or the absence of glucose in the perfusate. But in the presence of theophylline the response to arginine was normalized in the diabetics. Impairment of A cell function of the diabetics is not limited to recognition of amino-acids, since acetylcholine evoked a lower glucagon response in the diabetics than in the controls. These defects are different from those described in their B cells.
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PMID:Glucagon secretion in rats with non-insulin-dependent diabetes: an in vivo and in vitro study. 672 97

In this study the cardiovascular effects of diabetes consisted of a decrease in the heart rate 6 days and in the blood pressure 7 weeks after the induction of streptozotocin-diabetes in rats. The diabetes-induced decrease in heart rate was reversed within 4 days after the institution of insulin-treatment, which also prevented the fall in blood pressure. Maximal KC1 (70 mM) and phenylephrine (10(-4)M)-induced contractures in aortae from diabetic rats were 57 and 48%, respectively, of those from control animals, while tissues from insulin-treated diabetic rats did not differ from controls. Theophylline (10(-2)M)-induced relaxation of the phenylephrine contracture in diabetic tissues was less than in control aortae while relaxation of the K-contracture was greater in control than in diabetic tissues. Insulin-treatment reversed the effects of diabetes on theophylline-induced relaxation of the KC1, but not the phenylephrine contracture. These findings indicate that insulin-treatment will either prevent or reverse diabetes-induced decreases in blood pressure, heart rate and vascular responsiveness to phenylephrine and CK1.
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PMID:The effects of streptozotocin-induced diabetes and insulin-treatment on the cardiovascular system of the rat. 699 83

Galactomannan currently seems to be a very promising auxiliary. The aim of the present work was to examine the applicability of this auxiliary in tablet-making. Galactomannan is a polysaccharide composed of galactose and mannose, which is distributed by the Swiss firm Meyhall under the name Meyprogat. The products are numbered according to their molecular weight and polymeric degree. Thus, Meyprogat 7, 30, 60, 90, 120 and 150 can be discriminated. It is used in many areas, for example in the food industry as a stabilizing agent, and in medical therapy to cure diabetes and hyperlipidaemia. In pharmaceutical technology, it is used in low concentration (5-10%) as a disintegrant agent and in high concentration (25%) as binding agent. It is able to form a hydrophilic matrix, which results in sustained release. Theophylline was chosen as model agent. After the preformulation examinations, granulations were made by a wet method, and after this tablets were formed. Examinations were made of the granulations, the physical parameters of the tablets were determined, and the release of the effective agent from the tablets was studied. The following conclusions were drawn: 1. Galactomannan yields tablets with very good hardness. 2. Galactomannan is suitable for the formation of hydrophilic matrix tablets. Through use of this macromolecular agent, the rate of dissolution can be influenced in accordance with the desired purpose.
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PMID:[Use of galactomannan to produce hydrophilic matrix tablets]. 802 83


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