scholarly journals Effects of glucose and other modifiers of insulin release on the oxidative metabolism of amino acids in micro-dissected pancreatic islets

1971 ◽  
Vol 123 (4) ◽  
pp. 513-521 ◽  
Author(s):  
B. Hellman ◽  
J. Sehlin ◽  
I.-B. Täljedal
Keyword(s):  
Amino Acids ◽  
Glucose Metabolism ◽  
Cyclic Amp ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Β Cells ◽  
Insulin Secretagogues ◽  
Concentration Changes ◽  
Microdissected Pancreatic Islets ◽  
Oxidation Of Glucose

The oxidation of alanine, arginine, leucine, glucose, and pyruvate was studied in microdissected pancreatic islets of obese–hyperglycaemic mice. The following main observations were made. The oxidation of glucose was enhanced severalfold when its concentration was raised from 3 to 20mm. At the latter concentration the rate was about 65mmol/h per kg dry wt. The oxidation of 17mm-pyruvate amounted to 20mmol/h per kg dry wt. indicating a significant entry of this compound into the β-cells. Leucine oxidation was little affected by concentration changes above 5mm, the rate at 20mm corresponding to about 25% of that obtained with 20mm-glucose. In the absence of glucose, the oxidation of alanine or arginine was barely significant. Glucose stimulated the oxidation of alanine but depressed that of leucine. These effects of glucose were blocked by mannoheptulose or iodoacetamide but were not influenced by adrenaline, diazoxide, dibutyryl 3′:5′-cyclic AMP, or glibenclamide. The rate of alanine oxidation was doubled in the presence of 17mm-pyruvate but was unaffected by citrate or succinate. Succinate depressed the oxidation of leucine. Neither alanine nor leucine significantly affected the oxidation of glucose. It is suggested that the effects of glucose on the oxidation of alanine and leucine were mediated by metabolism of the sugar, and that amino acids do not act as insulin secretagogues by serving as fuels for the β-cells. The results are consistent with the existence of mechanisms auxiliary to glucose metabolism for control of insulin release.

scholarly journals The pentose cycle and insulin release in mouse pancreatic islets

1972 ◽  
Vol 126 (3) ◽  
pp. 525-532 ◽  
Author(s):  
S. J. H. Ashcroft ◽  
L. C. C. Weerasinghe ◽  
J. M. Bassett ◽  
P. J. Randle
Keyword(s):  
Glucose Metabolism ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Glucose Concentration ◽  
Glucose Utilization ◽  
Fold Increase ◽  
Primary Role ◽  
Mouse Pancreatic Islets ◽  
Oxidation Of Glucose

1. Rates of insulin release, glucose utilization (measured as [3H]water formation from [5-3H]glucose) and glucose oxidation (measured as14CO2 formation from [1-14C]- or [6-14C]-glucose) were determined in mouse pancreatic islets incubated in vitro, and were used to estimate the rate of oxidation of glucose by the pentose cycle pathway under various conditions. Rates of oxidation of [U-14C]ribose and [U-14C]xylitol were also measured. 2. Insulin secretion was stimulated fivefold when the medium glucose concentration was raised from 3.3 to 16.7mm in the absence of caffeine; in the presence of caffeine (5mm) a similar increase in glucose concentration evoked a much larger (30-fold) increase in insulin release. Glucose utilization was also increased severalfold as the intracellular glucose concentration was raised over this range, particularly between 5 and 11mm, but the rate of oxidation of glucose via the pentose cycle was not increased. 3. Glucosamine (20mm) inhibited glucose-stimulated insulin release and glucose utilization but not glucose metabolism via the pentose cycle. No evidence was obtained for any selective effect on the metabolism of glucose via the pentose cycle of tolbutamide, glibenclamide, dibutyryl 3′:5′-cyclic AMP, glucagon, caffeine, theophylline, ouabain, adrenaline, colchicine, mannoheptulose or iodoacetamide. Phenazine methosulphate (5μm) increased pentose-cycle flux but inhibited glucose-stimulated insulin release. 4. No formation of14CO2 from [U-14C]ribose could be detected: [U-14C]xylitol gave rise to small amounts of14CO2. Ribose and xylitol had no effect on the rate of oxidation of glucose; ribitol and xylitol had no effect on the rate of glucose utilization. Ribose, ribitol and xylitol did not stimulate insulin release under conditions in which glucose produced a large stimulation. 5. It is concluded that in normal mouse islets glucose metabolism via the pentose cycle does not play a primary role in insulin-secretory responses.

Lack of long-term β-cell glucotoxicity in vitro in pancreatic islets isolated from two mouse strains (C57BL/6J; C57BL/KsJ) with different sensitivities of the β-cells to hyperglycaemia in vivo

1993 ◽  
Vol 136 (2) ◽  
pp. 289-296 ◽  
Author(s):  
C. Svensson ◽  
S. Sandler ◽  
C. Hellerström
Keyword(s):  
Insulin Secretion ◽  
Glucose Metabolism ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Insulin Biosynthesis ◽  
Mouse Strains ◽  
Β Cells ◽  
Insulin Mrna

ABSTRACT Previous studies have shown that 4 weeks after syngeneic transplantation of a suboptimal number of islets into either C57BL/6J (BL/6J) or C57BL/KsJ (BL/KsJ) diabetic mice there is an impaired insulin secretion by the perfused grafts. After normalization of the blood glucose level with a second islet graft, the BL/6J strain showed restored insulin secretion whilst that of the BL/KsJ strain remained impaired. The aim of the present work was to study the effects of glucose on the in-vitro function of islet β-cells from these two mouse strains, with different sensitivities of their β-cells to glucose in vivo. Isolated pancreatic islets from each strain were kept for 1 week in tissue culture at 5·6, 11, 28 or 56 mmol glucose/l and were subsequently analysed with regard to insulin release, (pro)-insulin and total protein biosynthesis, insulin, DNA and insulin mRNA contents and glucose metabolism. Islets from both strains cultured at 28 or 56 mmol glucose/l showed an increased accumulation of insulin in the culture medium and an enhanced glucose-stimulated insulin release compared with corresponding control islets cultured at 11 mmol glucose/l. After culture at either 5·6 or 56 mmol/l, rates of (pro)insulin biosynthesis were decreased in BL/KsJ islets in short-term incubations at 17 mmol glucose/l, whereas islets cultured at 56 mmol glucose/l showed a marked increase at 1·7 mmol glucose/l. In BL/6J islets, the (pro)insulin biosynthesis rates were similar to those of the BL/KsJ islets with one exception, namely that no decrease was observed at 56 mmol glucose/l. Islets of both strains showed a decreased insulin content after culture with 56 mmol glucose/l. Insulin mRNA content was increased in islets cultured in 28 or 56 mmol glucose/l from both mouse strains. Glucose metabolism showed no differences in the rates of glucose oxidation, however, in islets cultured in 56 mmol glucose/l the utilization of glucose was increased in both BL/6J and BL/KsJ animals. There were no differences in DNA content in islets cultured at different glucose concentrations, suggesting no enhancement of cell death. The present study indicates that, irrespective of genetic background, murine β-cells can adapt to very high glucose concentrations in vitro without any obvious signs of so-called glucotoxicity. Previously observed signs of glucotoxicity in vivo in BL/KsJ islets appear not to be related only to glucose but rather to an additional factor in the diabetic environment. Journal of Endocrinology (1993) 136, 289–296

ON THE ACTION OF TOLBUTAMIDE IN NORMAL MAN

1973 ◽  
Vol 72 (3) ◽  
pp. 532-544 ◽  
Author(s):  
A. Widström ◽  
E. Cerasi
Keyword(s):  
Glucose Metabolism ◽  
Cyclic Amp ◽  
Insulin Release ◽  
Insulin Response ◽  
Phosphodiesterase Inhibitor ◽  
Adenyl Cyclase ◽  
Β Cells ◽  
Β Cell ◽  
Normal Man ◽  
Relationship Of

ABSTRACT Previous studies in normal man suggest that tolbutamide exerts its insulinogenic effect by modulating glucose-induced insulin release. This is probably achieved by increasing the sensitivity of the β-cells to the action of glucose in eliciting an insulinogenic signal, rather than by influencing the glucose metabolism of the islets. The present paper reports on studies on the relation of tolbutamide to the cyclic AMP system of the islets. Aminophylline, which decreases the breakdown of cyclic AMP, was without effect on tolbutamide-induced insulin release. This indicates that tolbutamide probably does not act by stimulating adenyl cyclase. In contrast, the insulin response to glucagon, an agent known to stimulate adenyl cyclase, was markedly potentiated by tolbutamide. Tolbutamide. in this respect, also showed synergism with arginine, which probably acts by enhancing the formation of cyclic AMP. It is therefore concluded that tolbutamide may influence insulin release by acting as a phosphodiesterase inhibitor or as a potentiator of the action of cyclic AMP on the release mechanisms. The possible relationship of the tolbutamide action with the postulated insulinogenic signal of glucose in the β-cell is discussed.

IONIC EFFECTS ON THE UPTAKE OF CHLOROMERCURIBENZENE-p-SULPHONIC ACID BY PANCREATIC ISLETS

1977 ◽  
Vol 86 (3) ◽  
pp. 552-560 ◽  
Author(s):  
Monica Söderberg ◽  
Inge-Bert Täljedal
Keyword(s):  
Pancreatic Islets ◽  
Islet Cell ◽  
Choline Chloride ◽  
Inorganic Ions ◽  
Sulphonic Acid ◽  
Cell Uptake ◽  
Β Cells ◽  
Sulphydryl Groups ◽  
Microdissected Pancreatic Islets ◽  
Ionic Effects

ABSTRACT Effects of inorganic ions on the uptake of chloromercuribenzene-p-sulphonic acid (CMBS) were studied in microdissected pancreatic islets of non-inbred ob/ob-mice. Na2SO4 stimulated the total islet cell uptake of CMBS but decreased the amount of CMBS remaining in islets after brief washing with L-cysteine. CaCl2 stimulated both the total and the cysteine-non-displaceable uptake; the stimulatory effect of CaCl2 on the cysteine-non-displaceable CMBS uptake was counteracted by Na2SO4. NaCl, KCl or choline chloride had no significant effect on the total islet cell uptake of CMBS, whereas LiCl was stimulatory. It is concluded that β-cells resemble erythrocytes in having a permeation path for CMBS that is inhibited by SO42−. By analogy with existing models of the erythrocyte membrane, it is suggested that the SO42−-sensitive path leads to sulphydryl groups controlling monovalent cationic permeability in β-cells.

Calcium-independent potentiation of insulin release by cyclic AMP in single β-cells

Nature ◽  
1993 ◽  
Vol 363 (6427) ◽  
pp. 356-358 ◽  
Author(s):  
Carina Ämmälä ◽  
Frances M. Ashcroft ◽  
Patrik Rorsman
Keyword(s):  
Cyclic Amp ◽  
Insulin Release ◽  
Β Cells

scholarly journals Regulation of glucokinase in pancreatic islets by prolactin: a mechanism for increasing glucose-stimulated insulin secretion during pregnancy

2007 ◽  
Vol 193 (3) ◽  
pp. 367-381 ◽  
Author(s):  
Anthony J Weinhaus ◽  
Laurence E Stout ◽  
Nicholas V Bhagroo ◽  
T Clark Brelje ◽  
Robert L Sorenson
Keyword(s):  
Insulin Secretion ◽  
Glucose Metabolism ◽  
Pancreatic Islets ◽  
Glucose Transporter ◽  
Β Cells ◽  
Glucose Transporter 2 ◽  
Underlying Mechanisms ◽  
Glucose Stimulated Insulin Secretion ◽  
Induced Changes

Glucokinase activity is increased in pancreatic islets during pregnancy and in vitro by prolactin (PRL). The underlying mechanisms that lead to increased glucokinase have not been resolved. Since glucose itself regulates glucokinase activity in β-cells, it was unclear whether the lactogen effects are direct or occur through changes in glucose metabolism. To clarify the roles of glucose metabolism in this process, we examined the interactions between glucose and PRL on glucose metabolism, insulin secretion, and glucokinase expression in insulin 1 (INS-1) cells and rat islets. Although the PRL-induced changes were more pronounced after culture at higher glucose concentrations, an increase in glucose metabolism, insulin secretion, and glucokinase expression occurred even in the absence of glucose. The presence of comparable levels of insulin secretion at similar rates of glucose metabolism from both control and PRL-treated INS-1 cells suggests the PRL-induced increase in glucose metabolism is responsible for the increase in insulin secretion. Similarly, increases in other known PRL responsive genes (e.g. the PRL receptor, glucose transporter-2, and insulin) were also detected after culture without glucose. We show that the upstream glucokinase promoter contains multiple STAT5 binding sequences with increased binding in response to PRL. Corresponding increases in glucokinase mRNA and protein synthesis were also detected. This suggests the PRL-induced increase in glucokinase mRNA and its translation are sufficient to account for the elevated glucokinase activity in β-cells with lactogens. Importantly, the increase in islet glucokinase observed with PRL is in line with that observed in islets during pregnancy.

Novel effects of insulin secretagogues on capacitation of insulin release and survival of cultured pancreatic islets

1990 ◽  
Vol 259 (4) ◽  
pp. E548-E554 ◽  
Author(s):  
M. J. MacDonald ◽  
L. A. Fahien ◽  
D. I. McKenzie ◽  
S. M. Moran
Keyword(s):  
Tissue Culture ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Metabolic Pathways ◽  
Time Course ◽  
Reciprocal Relationship ◽  
Insulin Secretagogues ◽  
Low Glucose ◽  
Islet Survival ◽  
Stimulate Insulin Release

Agents that stimulate insulin release from fresh pancreatic islets were tested for their ability to capacitate pancreatic islets to secrete insulin and to support beta-cell survival in tissue culture. Capacitation was defined as the ability to release insulin after 24 h in culture in the presence of an insulinotropic concentration of a secretagogue. Viable islets that lose glucose-induced insulin release gradually regain it during culture for 24 h in 20 mM glucose. Survival was defined as the ability to regain glucose-induced insulin release. To measure insulin release after culture, islets were incubated with various secretagogues in Krebs-Ringer buffer for 1 h. Examples of the diverse patterns of responses included the following. Glucose was the only secretagogue that capacitated glucose-induced release. Leucine-, leucine plus glutamine-, and glyceraldehyde-induced release remained capacitated after culture with no secretagogue. Culture at high glucose completely inhibited leucine-induced release. Culture at low glucose (1 mM) or at both high leucine and glutamine abolished glucose-induced release. Only leucine and glutamine capacitated monomethyl succinate-induced release. All agents including subinsulinotropic glucose (1 mM), except D-glyceraldehyde, permitted islet survival. Thus the metabolic pathways for initiation, capacitation, and survival are not identical between and within secretagogues. There is a reciprocal relationship between leucine and glucose with respect to capacitation. Capacitation follows a time course, which suggests that it is regulated by enzyme induction.

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