Evidence that a 'memory' for glucose metabolism desensitizes A-cell responsiveness in the perfused pancreas of the rat

1985 ◽  
Vol 110 (1) ◽  
pp. 114-119
Author(s):  
V. Grill ◽  
M. Rundfeldt ◽  
S. Efendić
Keyword(s):  
Glucose Concentration ◽  
Glucagon Secretion ◽  
Energy Availability ◽  
High Glucose Concentration ◽  
Perfused Pancreas ◽  
Total Response ◽  
Cell Sensitivity ◽  
Elevated Glucose ◽  
Cell Energy ◽  
A Cell

Abstract. The effects of prior exposure to glucose or an inhibitor of glycolysis (iodoacetate) on A-cell sensitivity to glucose in the perfused pancreas of the rat was investigated. Inhibition of glucagon secretion by a high glucose concentration (22 mm) was attenuated and delayed when tested 20 min after a previous infusion with the same glucose concentration. Previously elevated glucose also delayed for 2 min a glucagon response to glucose omission whereas the total response was not significantly affected. During a 20 min perfusion with 1 mm iodoacetate, glucagon secretion increased and rates of secretion were further augmented after withdrawal of iodoacetate. When introduced 10 min after cessation of the iodoacetate pulse, 22 mm glucose failed to affect insulin or somatostatin release but, conversely, induced a profound decrease in glucagon secretion which was more marked than during control conditions. Conclusions: A-cell sensitivity to glucose is diminished and enhanced by prior fuel abundance and deprivation, respectively. Such effects could be due to persisting changes in A-cell energy availability rather than to pertubations in insulin or somatostatin secretion.

α- and β-Cell Function in Obese Zucker (fa/fa) Rats: A Study with the Isolated Perfused Pancreas

1994 ◽  
Vol 86 (3) ◽  
pp. 311-316 ◽  
Author(s):  
Dr Hiroshi Hirose ◽  
Hiroshi Maruyama ◽  
Koichi Kido ◽  
Katsuhiko Ito ◽  
Kazunori Koyama ◽  
...  
Keyword(s):  
Glucose Concentration ◽  
Cell Function ◽  
Glucagon Secretion ◽  
Zucker Rats ◽  
Perfused Pancreas ◽  
Isolated Perfused Pancreas ◽  
Insulin And Glucagon Secretion ◽  
Β Cell Function ◽  
Insulin Secretion Rate ◽  
Insulin Secretory Response

1. The effects of various stimuli, including changes in glucose concentration, arginine, tyramine and noradrenaline, on insulin and glucagon secretion were investigated using isolated perfused pancreata of obese and lean male Zucker rats at 12 months of age. 2. In Zucker fatty rats, the insulin secretion rate was significantly (P < 0.01) higher than that of lean rats at all glucose concentrations tested (8.3, 16.7 and 1.4 mmol/l). However, the integrated insulin secretory response to raising the glucose concentration from 8.3 to 16.7 mmol/l was almost absent in these rats. The glucagon secretion rates were significantly lower at 8.3 and 1.4 mmol/l glucose (P < 0.001 for both), and in responses to 10 μg/ml tyramine and 0.1 μmol/l noradrenaline (P < 0.05 for both), in Zucker fatty rats. Integrated insulin and glucagon responses to 10 mmol/l arginine were identical in the two groups. 3. Histopathological and immunochemical studies revealed hyperplasia of β-cells and scattered α-cells in the enlarged islets of Zucker fatty rats. 4. These results suggest that, in Zucker fatty rats, the decreased glucagon secretion in the isolated perfused pancreas is attributable to changes in the environment of α-cells and/or the inhibitory effects of hypersecreted insulin.

scholarly journals Involvement of glucokinase translocation in the mechanism by which resorcinol inhibits glycolysis in hepatocytes

1997 ◽  
Vol 325 (3) ◽  
pp. 667-673 ◽  
Author(s):  
Loranne AGIUS
Keyword(s):  
Glucose Concentration ◽  
Glycogen Synthesis ◽  
High Glucose Concentration ◽  
Phosphate Content ◽  
Maximal Inhibition ◽  
Independent Mechanism ◽  
Elevated Glucose ◽  
Inhibition Of Glycolysis ◽  
Low Activity ◽  
Stimulation Of

Proglycosyn and resorcinol stimulate glycogen synthesis and inhibit glycolysis in hepatocytes. The former effect is attributed to inactivation of phosphorylase mediated by glucuronidated metabolites. This study investigated the mechanism by which resorcinol inhibits glycolysis. Resorcinol (150 μM) inhibited glycolysis in hepatocytes incubated with glucose (15–35 mM) but not with dihydroxyacetone (10 mM). The inhibition of glycolysis at elevated glucose concentration was associated with inhibition of glucose-induced dissociation of glucokinase and aldolase. The resorcinol concentration that caused half-maximal inhibition (20–43 μM) increased with increasing glucose concentration (15–35 mM). Resorcinol inhibited the translocation of glucokinase and the stimulation of detritiation of [2-3H]glucose and [3-3H]glucose caused by sorbitol (10–200 μM), but it potentiated the stimulation of glycogen synthesis. The inhibition of glycolysis by resorcinol could not be accounted for by diversion of substrate to glycogen. The glucose 6-phosphate content correlated with the free glucokinase activity. Resorcinol counteracted the increase in glucose 6-phosphate and fructose 2,6-bisphosphate caused by elevated glucose concentration or by sorbitol. The suppression of glucose 6-phosphate at high glucose concentration (15–35 mM) could be explained by the low activity of free glucokinase. However, the suppression at 5 mM glucose was due in part to an independent mechanism. The effect of resorcinol on glucokinase translocation was partly counteracted by galactosamine, which suppresses UDP-glucose and inhibits glucuronide formation, and was mimicked by phenol and p-nitrophenol but not by p-nitrophenylglucuronide. It is concluded that resorcinol inhibits glycolysis at elevated glucose concentration or when stimulated by sorbitol through increased glucokinase binding. The results indicate a link between glucuronidation and glucokinase translocation.

STIM1/Orai1 Inhibition Reduces Store-Operated Ca2+Entry and Modulates a-Cell Glucagon Secretion

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 2174-P
Author(s):  
MOLLY K. ALTMAN ◽  
PRASANNA DADI ◽  
DAVID JACOBSON
Keyword(s):  
Glucagon Secretion ◽  
A Cell

High glucose concentration suppresses mesangial laminin B2 gene expression

1991 ◽  
Vol 5 (2-3) ◽  
pp. 118-120 ◽  
Author(s):  
Shigehiro Katayama ◽  
Mari Abe ◽  
Kiyoshi Tanaka ◽  
Akira Omoto ◽  
Kiyohiko Negishi ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Glucose ◽  
Glucose Concentration ◽  
High Glucose Concentration

scholarly journals Sulodexide reduces glucose induced senescence in human retinal endothelial cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
A. Gericke ◽  
K. Suminska-Jasińska ◽  
A. Bręborowicz
Keyword(s):  
Endothelial Cells ◽  
High Glucose ◽  
Glucose Concentration ◽  
Chronic Exposure ◽  
Replicative Senescence ◽  
Population Doubling ◽  
Population Doubling Time ◽  
High Glucose Concentration ◽  
Retinal Endothelial Cells

AbstractChronic exposure of retinal endothelium cells to hyperglycemia is the leading cause of diabetic retinopathy. We evaluated the effect of high glucose concentration on senescence in human retinal endothelial cells (HREC) and modulation of that effect by Sulodexide. Experiments were performed on HREC undergoing in vitro replicative senescence in standard medium or medium supplemented with glucose 20 mmol/L (GLU) or mannitol 20 mnol/L (MAN). Effect of Sulodexide 0.5 LRU/mL (SUL) on the process of HREC senescence was studied. Glucose 20 mmol/L accelerates senescence of HREC: population doubling time (+ 58%, p < 0.001) β-galactosidase activity (+ 60%, p < 0.002) intracellular oxidative stress (+ 65%, p < 0.01), expression of p53 gene (+ 118%, p < 0.001). Senescent HREC had also reduced transendothelial electrical resistance (TEER) (− 30%, p < 0.001). Mannitol 20 mmol/L used in the same scenario as glucose did not induce HREC senescence. In HREC exposed to GLU and SUL, the senescent changes were smaller. HREC, which became senescent in the presence of GLU, demonstrated higher expression of genes regulating the synthesis of Il6 and VEGF-A, which was reflected by increased secretion of these cytokines (IL6 + 125%, p < 0.001 vs control and VEGF-A + 124% p < 0.001 vs control). These effects were smaller in the presence of SUL, and additionally, an increase of TEER in the senescent HREC was observed. Chronic exposure of HREC to high glucose concentration in medium accelerates their senescence, and that process is reduced when the cells are simultaneously exposed to Sulodexide. Additionally, Sulodexide decreases the secretion of IL6 and VEGF-A from senescent HREC and increases their TEER.

Impact of lack of suppression of glucagon on glucose tolerance in humans

1999 ◽  
Vol 277 (2) ◽  
pp. E283-E290 ◽  
Author(s):  
Pankaj Shah ◽  
Ananda Basu ◽  
Rita Basu ◽  
Robert Rizza
Keyword(s):  
Insulin Secretion ◽  
Glucose Concentration ◽  
Cell Function ◽  
Hormone Secretion ◽  
Glucose Production ◽  
Glucagon Secretion ◽  
Β Cell ◽  
Β Cell Function ◽  
Glucagon Suppression

People with type 2 diabetes have defects in both α- and β-cell function. To determine whether lack of suppression of glucagon causes hyperglycemia when insulin secretion is impaired but not when insulin secretion is intact, twenty nondiabetic subjects were studied on two occasions. On both occasions, a “prandial” glucose infusion was given over 5 h while endogenous hormone secretion was inhibited. Insulin was infused so as to mimic either a nondiabetic ( n = 10) or diabetic ( n = 10) postprandial profile. Glucagon was infused at a rate of 1.25 ng ⋅ kg−1 ⋅ min−1, beginning either at time zero to prevent a fall in glucagon (nonsuppressed study day) or at 2 h to create a transient fall in glucagon (suppressed study day). During the “diabetic” insulin profile, lack of glucagon suppression resulted in a marked increase ( P < 0.002) in both the peak glucose concentration (11.9 ± 0.4 vs. 8.9 ± 0.4 mmol/l) and the area above basal of glucose (927 ± 77 vs. 546 ± 112 mmol ⋅ l−1 ⋅ 6 h) because of impaired ( P < 0.001) suppression of glucose production. In contrast, during the “nondiabetic” insulin profile, lack of suppression of glucagon resulted in only a slight increase ( P< 0.02) in the peak glucose concentration (9.1 ± 0.4 vs. 8.4 ± 0.3 mmol/l) and the area above basal of glucose (654 ± 146 vs. 488 ± 118 mmol ⋅ l−1 ⋅ 6 h). Of interest, when glucagon was suppressed, glucose concentrations differed only minimally during the nondiabetic and diabetic insulin profiles. These data indicate that lack of suppression of glucagon can cause substantial hyperglycemia when insulin availability is limited, therefore implying that inhibitors of glucagon secretion and/or glucagon action are likely to be useful therapeutic agents in such individuals.

scholarly journals The influence of high glucose concentration on the ability of mesenchymal stromal cells to stimulate blood vessel growth

2011 ◽  
Vol 14 (2) ◽  
pp. 32-35 ◽  
Author(s):  
Zhanna Alekseevna Akopyan ◽  
Georgy Vladimirovich Sharonov ◽  
Tatiana Nikolaevna Kochegura ◽  
Natalya Fedorovna Il'yashenko ◽  
Igor Eduardovich Belyanko ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Blood Vessel ◽  
High Glucose ◽  
Glucose Concentration ◽  
Functional Activity ◽  
Human Adipose Tissue ◽  
Diabetic Patients ◽  
High Glucose Concentration ◽  
Vessel Growth ◽  
Negative Effect

Adipose issue is a source of mesenchymal stem cells (MSC) that can be used to stimulate blood vessel growth in ischemic tissues. Various metabolicdisorders including hypeglycemia may have negative effect on therapeutic properties of these cells. Aim. To study the influence of high glucose concentration on functional activity in human adipose tissue. Materials and methods. Flow cytometry and real time PCR were used to study functional activity of cultured MSC from human adipose issue at highglucose concentration. Results. Prolonged (10-12 days) incubation at a high glucose concentration (25 mM) suppressed the ability of MSC to stimulate angiogenesis. Also,glucose modified expression of genes activating and inhibiting angiogenesis but had no effect on MSC proliferation and apoptosis. Conclusion. High glucose concentration suppresses angiogenic activity of MSC in adipose tissue; it may account for incomplete restoration of bloodflow in diabetic patients.

scholarly journals Successful Continuation of Peritoneal Dialysis after "Sweet" Hydrothorax

2015 ◽  
Vol 13 (1) ◽  
pp. 42-45
Author(s):  
Utku Erdem Soyaltin ◽  
Ferhat Ekinci ◽  
Denizhan Ayatan ◽  
Cihangir Turemis ◽  
Mustafa Yildirim ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Glucose Concentration ◽  
Serum Glucose ◽  
X Ray ◽  
Glucose Levels ◽  
Low Protein ◽  
Elevated Glucose ◽  
Chest X Ray ◽  
Stage Renal Disease ◽  
End Stage

AbstractA 44-year-old woman with end-stage renal disease presented with dyspnea on exertion and a vague chest pain about two weeks after commencing continuous ambulatory peritoneal dialysis (CAPD) four months ago. A chest x-ray revealed massive unilateral right-sided pleural effusion. Laboratory analysis of the effusion revealed low protein and lactate dehydrogenase but elevated glucose levels were consistent with transudate and pleuroperitoneal leakage. Pleural glucose concentration was much higher than patients’ serum glucose concentration, which was suggestive of "sweet" hydrothorax because of this high glucose concentration. It is advisable to keep this condition in mind among the differenttial diagnoses of hydrothorax in patients on CAPD.

Somatostatin, insulin and glucagon secretion by the perfused pancreas from the cysteamine-treated rat

1986 ◽  
Vol 134 (3) ◽  
pp. 1291-1297 ◽  
Author(s):  
R.A. Silvestre ◽  
P. Miralles ◽  
P. Moreno ◽  
M.L. Villanueva ◽  
J. Marco
Keyword(s):  
Glucagon Secretion ◽  
Perfused Pancreas ◽  
Insulin And Glucagon Secretion
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