Effect of 7 days of bed rest on dose-response relation between plasma glucose and insulin secretion

1989 ◽  
Vol 257 (1) ◽  
pp. E43-E48 ◽  
Author(s):  
K. J. Mikines ◽  
F. Dela ◽  
B. Tronier ◽  
H. Galbo
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Insulin Response ◽  
Bed Rest ◽  
Glucose Disposal ◽  
Cell Secretion ◽  
Hyperglycemic Clamp ◽  
Peripheral Insulin Resistance ◽  
Glucose Stimulated Insulin Secretion ◽  
Beta Cell Secretion

Physical training decreases glucose-stimulated insulin secretion. To further explore the influence of the level of daily physical activity on beta-cell secretion, the effect of 7 days of bed rest was studied in six young, healthy men by sequential hyperglycemic clamp technique (7, 11, and 20 mM glucose, each step lasting 90 min). At 11 and 20 mM glucose, insulin concentrations in plasma were higher after (87 +/- 11 and 303 +/- 63 microU/ml) than before (63 +/- 5 and 251 +/- 50 microU/ml, P less than 0.05) bed rest. Also C-peptide levels were higher after bed rest than before during glucose stimulation. The responses of other hormones, metabolites, or electrolytes influencing beta-cell secretion were not influenced by bed rest. In spite of increased insulin levels after bed rest, glucose disposal at 20 mM of glucose was significantly lower after bed rest than before. It is concluded that bed rest for 7 days increases the glucose-stimulated insulin response, at least partly due to a beta-cell adaptation increasing glucose-stimulated insulin secretion. However, the insulin secretion does not increase adequately compared with the peripheral insulin resistance induced by bed rest.

Diminished arginine-stimulated insulin secretion in trained men

1990 ◽  
Vol 69 (1) ◽  
pp. 261-267 ◽  
Author(s):  
F. Dela ◽  
K. J. Mikines ◽  
B. Tronier ◽  
H. Galbo
Keyword(s):  
Growth Hormone ◽  
Insulin Secretion ◽  
Beta Cell ◽  
Insulin Response ◽  
Cell Secretion ◽  
Cell Adaptation ◽  
Glucose Stimulated Insulin Secretion ◽  
Beta Hydroxybutyrate ◽  
Beta Cell Adaptation ◽  
Beta Cell Secretion

Glucose-stimulated insulin secretion is depressed by training. To further elucidate the beta-cell adaptation to training, a nonglucose secretagogue was applied. Arginine was infused for 90 min to seven trained and seven untrained young men. Arginine and glucose concentrations increased identically in the groups. The insulin response was biphasic and waned despite increasing arginine concentrations. Both these phases as well as C-peptide responses were reduced in trained subjects, whereas proinsulin responses were similar in the groups. Identical increases were found in glucagon, growth hormone, catecholamines, and production and disappearance of glucose; identical decreases were found in free fatty acids, glycerol, and beta-hydroxybutyrate. In conclusion, in men training diminishes both arginine- and glucose-stimulated insulin secretion, indicating a profound beta-cell adaptation. Being enhanced, the effects of insulin on both production and disposal of glucose are changed in the opposite direction to beta-cell secretion by training. The responses of glucagon- and growth hormone-secreting cells to arginine do not change with training.

Effects of treadmill exercise to exhaustion on the insulin response to hyperglycemia in untrained men

1991 ◽  
Vol 70 (1) ◽  
pp. 246-250 ◽  
Author(s):  
J. P. Kirwan ◽  
R. E. Bourey ◽  
W. M. Kohrt ◽  
M. A. Staten ◽  
J. O. Holloszy
Keyword(s):  
Insulin Secretion ◽  
Early Phase ◽  
Pancreatic Beta Cell ◽  
Late Phase ◽  
Insulin Response ◽  
Creatine Kinase Activity ◽  
Whole Body ◽  
Glucose Disposal ◽  
C Peptide ◽  
Hyperglycemic Clamp

The effects of a single bout of exercise to exhaustion on pancreatic insulin secretion were determined in seven untrained men by use of a 3-h hyperglycemic clamp with plasma glucose maintained at 180 mg/100 ml. Clamps were performed either 12 h after an intermittent treadmill run at approximately 77% maximum O2 consumption or without prior exercise. Arterialized blood samples for glucose, insulin, and C-peptide determination were obtained from a heated hand vein. The peak insulin response during the early phase (0–10 min) of the postexercise clamp was higher (81 +/- 8 vs. 59 +/- 9 microU/ml; P less than 0.05) than in the nonexercise clamp. Incremental areas under the insulin (376 +/- 33 vs. 245 +/- 51 microU.ml-1.min) and C-peptide (17 +/- 2 vs. 12 +/- 1 ng.ml-1.min) curves were also greater (P less than 0.05) during the early phase of the postexercise clamp. No differences were observed in either insulin concentrations or whole body glucose disposal during the late phase (15–180 min). Area under the C-peptide curve was greater during the late phase of the postexercise clamp (650 +/- 53 vs. 536 +/- 76 ng.ml-1.min, P less than 0.05). The exercise bout induced muscle soreness and caused an elevation in plasma creatine kinase activity (142 +/- 32 vs. 305 +/- 31 IU/l; P less than 0.05) before the postexercise clamp. We conclude that in untrained men a bout of running to exhaustion increased pancreatic beta-cell insulin secretion during the early phase of the hyperglycemic clamp. Increased insulin secretion during the late phase of the clamp appeared to be compensated by increased insulin clearance.

scholarly journals Beta cell secretion of miR-375 to HDL is inversely associated with insulin secretion

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Leslie R. Sedgeman ◽  
Carine Beysen ◽  
Marisol A. Ramirez Solano ◽  
Danielle L. Michell ◽  
Quanhu Sheng ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Cell Secretion ◽  
Beta Cell Secretion

Effects of training and detraining on dose-response relationship between glucose and insulin secretion

1989 ◽  
Vol 256 (5) ◽  
pp. E588-E596 ◽  
Author(s):  
K. J. Mikines ◽  
B. Sonne ◽  
B. Tronier ◽  
H. Galbo
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Plasma Glucose ◽  
Response Relationship ◽  
Cell Secretion ◽  
Dose Response Relationship ◽  
C Peptide ◽  
Endogenous Insulin ◽  
Beta Cell Secretion ◽  
Training And Detraining

We studied the effect of training and detraining on the dose-response relationship between plasma glucose and beta-cell secretion in seven trained young men using sequential hyperglycemic clamp technique (7, 11, and 20 mM). Experiments were performed in the habitual state 15 h after last training session (T) as well as after 5 days of detraining (DT). Results were compared to data from seven untrained subjects (UT). Glucose-stimulated insulin, proinsulin, and C-peptide levels were lower in T than in UT. They increased during detraining but not to levels seen in UT. Furthermore, in T and DT, but not in UT, increases in C-peptide and proinsulin leveled off with increasing glucose concentrations. Estimated by C-peptide-to-insulin ratios, clearance of endogenous insulin was not influenced by T. Glucose uptake in tissue was the same in T, DT, and UT during clamps, despite lower insulin levels in T and DT. Differences between groups in counterregulatory hormones, fat metabolites, alanine, or electrolytes did not account for these findings. Oxygen consumption was higher in the basal state in T and DT compared with UT but increased similarly in all groups in response to glucose. Conclusions: regular physical activity causes an adaptive decrease in glucose-mediated beta-cell secretion in humans. The training-induced decrease in glucose-stimulated insulin secretion is accurately matched to increased insulin action, keeping glucose disposal constant at any given plasma glucose concentration. Finally, training increases basal metabolic rate but does not influence glucose-induced thermogenesis or clearance of endogenous insulin.

Effects of eccentric exercise on insulin secretion and action in humans

1993 ◽  
Vol 75 (5) ◽  
pp. 2151-2156 ◽  
Author(s):  
D. S. King ◽  
T. L. Feltmeyer ◽  
P. J. Baldus ◽  
R. L. Sharp ◽  
J. Nespor
Keyword(s):  
Insulin Secretion ◽  
Eccentric Exercise ◽  
Plasma Glucose ◽  
Early Phase ◽  
Pancreatic Beta Cell ◽  
Late Phase ◽  
Insulin Response ◽  
Whole Body ◽  
Glucose Disposal ◽  
Hyperglycemic Clamp

The effects of an exhaustive bout of eccentric exercise on insulin secretion and action were determined using the hyperglycemic clamp technique. Clamps were performed on eight healthy men after 7 days of inactivity and approximately 36 h after a bout of eccentric exercise. Eccentric exercise consisted of 10 sets of 10 repetitions of combined knee extensions and flexions for each leg at a mean torque 84 +/- 5% of peak concentric torque. During the hyperglycemic clamp procedure, plasma glucose concentration was acutely raised to 10 mmol/l and was maintained near this level for 120 min. Arterialized blood samples were obtained from a heated hand vein to determine plasma glucose and insulin concentrations. Eccentric exercise appeared to produce marked muscle damage, as indicated by a 50-fold increase in plasma creatine phosphokinase (100 +/- 17 vs. 5,209 +/- 3,811 U/l, P < 0.001) and subjective reports of muscle soreness. Peak insulin response during the early phase (0–10 min) of the hyperglycemic clamp was higher after eccentric exercise (183 +/- 38 microU/ml) than after the control clamp (100 +/- 23 microU/ml, P < 0.005). Late-phase (10- to 120-min) insulin response was not altered after eccentric exercise. Peak plasma C-peptide concentrations were higher during the early phase (5.0 +/- 0.7 vs. 4.3 +/- 0.8 ng/ml, P < 0.05) and the late phase (7.5 +/- 0.9 vs. 5.4 +/- 0.6 ng/ml, P < 0.05). Prior eccentric exercise had no significant effect on whole body glucose disposal or glucose disposal rate adjusted for prevailing plasma insulin concentration. These data provide evidence that a single bout of eccentric exercise causes an increase in pancreatic beta-cell insulin secretion in response to hyperglycemia.

scholarly journals Increased Slc12a1 expression in β-cells and improved glucose disposal in Slc12a2 heterozygous mice

2015 ◽  
Vol 227 (3) ◽  
pp. 153-165 ◽  
Author(s):  
Saeed Alshahrani ◽  
Mohammed Mashari Almutairi ◽  
Shams Kursan ◽  
Eduardo Dias-Junior ◽  
Mohamed Mahmoud Almiahuob ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Response ◽  
Chloride Concentration ◽  
Glucose Disposal ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Glucose Levels ◽  
Fasting Glycemia ◽  
Blood Glucose Levels ◽  
Glucose Stimulated Insulin Secretion

The products of theSlc12a1andSlc12a2genes, commonly known as Na+-dependent K+2Cl−co-transporters NKCC2 and NKCC1, respectively, are the targets for the diuretic bumetanide. NKCCs are implicated in the regulation of intracellular chloride concentration ([Cl−]i) in pancreatic β-cells, and as such, they may play a role in glucose-stimulated plasma membrane depolarization and insulin secretion. Unexpectedly, permanent elimination of NKCC1 does not preclude insulin secretion, an event potentially linked to the homeostatic regulation of additional Cl−transporters expressed in β-cells. In this report we provide evidence for such a mechanism. Mice lacking a single allele ofSlc12a2exhibit lower fasting glycemia, increased acute insulin response (AIR) and lower blood glucose levels 15–30 min after a glucose load when compared to mice harboring both alleles of the gene. Furthermore, heterozygous expression or complete absence ofSlc12a2associates with increased NKCC2 protein expression in rodent pancreatic β-cells. This has been confirmed by using chronic pharmacological down-regulation of NKCC1 with bumetanide in the mouse MIN6 β-cell line or permanent molecular silencing of NKCC1 in COS7 cells, which results in increased NKCC2 expression. Furthermore, MIN6 cells chronically pretreated with bumetanide exhibit increased initial rates of Cl−uptake while preserving glucose-stimulated insulin secretion. Together, our results suggest that NKCCs are involved in insulin secretion and that a singleSlc12a2allele may protect β-cells from failure due to increased homeostatic expression ofSlc12a1.

Effects of physiologic and supraphysiologic hyperglycemia on early and late-phase insulin secretion in chronically dialyzed uremic patients

1989 ◽  
Vol 121 (2) ◽  
pp. 251-258 ◽  
Author(s):  
Ole Schmitz
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Serum Insulin ◽  
Late Phase ◽  
Insulin Response ◽  
Glucose Disposal ◽  
Insulin Resistant ◽  
Normal Glucose ◽  
Glucose Challenge ◽  
Uremic Patients

Abstract. To test secretory capacity of the beta-cell to a glucose stimulus in uremic patients on chronic dialysis, three hyperglycemic clamps (plasma glucose increments: 1, 4.5 and 11 mmol/l) were performed in 8 uremic and 8 healthy subjects. Early-phase insulin and C-peptide responses (ΔI and ΔC) during the initial 6 min were consistently exaggerated at all three steps in uremic patients compared with controls (ΔI. 16 ± 4 vs 4 ± 2, 41 ± 11 vs 15 ± 4 and 60 ± 12 vs 24 ± 5 mU/l; ΔC. 0.39 ± 0.13 vs 0.07 ± 0.02, 0.40 ± 0.13 vs 0.16 ± 0.02 and 0.73 ± 0.15 vs 0.29 ± 0.04 nmol/l, p < 0.05 in all cases). Similarly, late-phase insulin secretion defined as the insulin increment between 90 and 120 min after initiation of the glucose challenge was enhanced in uremic patients at the two highest glycemic steps (44 ± 10 vs 16 ± 2 and 123 ± 29 vs 44 ± 5 mU/l, both p < 0.01). The raised late-phase insulin response allowed comparable glucose disposal in the two groups (uremic patients: 9.2 ± 1.0 and 15.5 ± 1.6 mg · kg−1 · min−1· Controls: 9.0 ± 1.3 and 19.9 ± 2.4 mg · kg−1 · min−1). The slopes of potentiation, i.e. the slopes of the regression lines expressing the relationship between changes in insulin increments and changes in glucose, were markedly steeper in uremic patients (0.45 ± 0.09 and 0.66 ± 0.20, early and late-phase respectively) than in controls (0.20 ± 0.06 and 0.25 ± 0.03). No relationship between serum insulin responses and electrolytes or PTH was demonstrated. In conclusion, despite several factors which may inhibit the ability of the beta-cell to respond to a glucose stimulus, acute hyperglycemia elicits in insulin-resistant uremic subjects an exaggerated early and late-phase insulin secretion which is able to compensate for insulin resistance, thereby maintaining normal glucose disposal.

scholarly journals A reduced incretin effect mediated by the rs7903146 variant in the TCF7L2 Gene is an early marker of beta-cell dysfunction in obese youth

2020 ◽  
Author(s):  
Alfonso Galderisi ◽  
Domenico Trico ◽  
Bridget Pierpont ◽  
Veronika Shabanova ◽  
Stephanie Samuels ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Beta Cell ◽  
Plasma Glucose ◽  
Metabolic Phenotype ◽  
Glucose Disposal ◽  
Incretin Effect ◽  
Tcf7l2 Gene ◽  
Intravenous Glucose ◽  
Hyperglycemic Clamp

<b>Background.</b> The risk genotype for the common variant <i>rs7903146 </i>of the transcription factor-7-like-2 gene (<i>TCF7L2</i>) has been found to affect the incretin response in healthy and obese adults, however, whether a similar functional defect is also present in obese adolescents remains unexplored. Herein, we examined the functional effect of the <i>rs7903146</i> variant in the TCF7L2 gene on the incretin effect and determined its translational metabolic manifestation by performing deep phenotyping of the incretin system, beta-cell function relative to insulin sensitivity, the Gastrointestinal Induced Glucose Disposal (GIGD) in obese youths with normal and impaired glucose tolerance. <p><b>Methods</b> Thirty nine non-diabetic obese adolescents (15[14,18] years; BMI 37[33, 43]kg/m<sup>2</sup>) were genotyped for the <i>rs7903146 </i>of <i>TCF7L2</i> and underwent a 3-hour OGTT followed by an iso-glycemic intravenous glucose infusion (iso-IVGTT) to match the plasma glucose concentrations during the OGTT and a hyperglycemic clamp with arginine stimulation.</p> <p>The incretin effect was measured as 100*(AUC-SR<sub>OGTT </sub>– AUC-SR<sub>iso-IVGTT</sub>)/AUC-SR<sub>OGTT </sub>[AUC-SR=AUC of C-peptide secretion rate]. Participants were grouped into tertiles according to the percentage incretin effect (High-, Moderate- and Low-incretin effect) to describe their metabolic phenotype.</p> <p><b>Results </b>The presence of T risk allele for <i>TCF7L2</i> was associated with a markedly reduced </p> <p>incretin effect compared to the wild type genotype(0.3[-7.2,14] vs 37.8[12.5-52.4], p<0.002) When the cohort was stratified by incretin effect, the High-, Moderate- and Low-incretin groups did not differ with respect to anthropometric features, while the Low-incretin group exhibited higher 1-h glucose (p=0.015), a reduced disposition index, insulin sensitivity and insulin clearance, compared with the High-incretin group. Gastrointestinal induced glucose disposal (GIGD) was reduced in the Low-incretin group (p=0.001). The three groups did not differ with respect to intravenous glucose-induced insulin secretion and arginine response during the hyperglycemic clamp. </p> <p><b>Conclusion </b>A<b> </b> reduced incretin effect and its association with the <i>TCF7L2</i> variant rs7903146 identify an early metabolic phenotype in obese non-diabetic youths, featured by a higher plasma glucose peak at 1hr, lower insulin secretion, sensitivity and clearance, and gastrointestinal glucose disposal. </p>

Acute lowering of circulating fatty acids improves insulin secretion in a subset of type 2 diabetes subjects

2003 ◽  
Vol 284 (1) ◽  
pp. E129-E137 ◽  
Author(s):  
Elisabeth Qvigstad ◽  
Ingrid L. Mostad ◽  
Kristian S. Bjerve ◽  
Valdemar E. Grill
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Insulin Secretion ◽  
Dietary Intervention ◽  
Insulin Response ◽  
Low Fat Diet ◽  
Hyperglycemic Clamp ◽  
Glucose Stimulated Insulin Secretion ◽  
Secretion Rates

We tested the effects of acute perturbations of elevated fatty acids (FA) on insulin secretion in type 2 diabetes. Twenty-one type 2 diabetes subjects with hypertriglyceridemia (triacylglycerol >2.2 mmol/l) and 10 age-matched nondiabetic subjects participated. Glucose-stimulated insulin secretion was monitored during hyperglycemic clamps for 120 min. An infusion of Intralipid and heparin was added during minutes 60–120. In one of two tests, the subjects ingested 250 mg of Acipimox 60 min before the hyperglycemic clamp. A third test (also with Acipimox) was performed in 17 of the diabetic subjects after 3 days of a low-fat diet. Acipimox lowered FA levels and enhanced insulin sensitivity in nondiabetic and diabetic subjects alike. Acipimox administration failed to affect insulin secretion rates in nondiabetic subjects and in the group of diabetic subjects as a whole. However, in the diabetic subjects, Acipimox increased integrated insulin secretion rates during minutes 60–120 in the 50% having the lowest levels of hemoglobin A1c (379 ± 34 vs. 326 ± 30 pmol · kg−1 · min−1without Acipimox, P < 0.05). A 3-day dietary intervention diminished energy from fat from 39 to 23% without affecting FA levels and without improving the insulin response during clamps. Elevated FA levels may tonically inhibit stimulated insulin secretion in a subset of type 2 diabetic subjects.

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