scholarly journals Restoration of Glucose-Stimulated Cdc42-Pak1 Activation and Insulin Secretion by a Selective Epac Activator in Type 2 Diabetic Human Islets

Diabetes ◽  
2018 ◽  
Vol 67 (10) ◽  
pp. 1999-2011 ◽  
Author(s):  
Rajakrishnan Veluthakal ◽  
Oleg G. Chepurny ◽  
Colin A. Leech ◽  
Frank Schwede ◽  
George G. Holz ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Human Islets ◽  
Pak1 Activation ◽  
Type 2 Diabetic

scholarly journals Acute Alcohol Consumption Improves Insulin Action Without Affecting Insulin Secretion in Type 2 Diabetic Subjects

Diabetes Care ◽  
2004 ◽  
Vol 27 (6) ◽  
pp. 1369-1374 ◽  
Author(s):  
A. Avogaro ◽  
R. M. Watanabe ◽  
A. Dall'Arche ◽  
S. Vigili De Kreutzenberg ◽  
A. Tiengo ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Alcohol Consumption ◽  
Insulin Action ◽  
Type 2 Diabetic

Dynamics of glucose-induced insulin secretion in normal human islets

2015 ◽  
Vol 309 (7) ◽  
pp. E640-E650 ◽  
Author(s):  
Jean-Claude Henquin ◽  
Denis Dufrane ◽  
Julie Kerr-Conte ◽  
Myriam Nenquin
Keyword(s):  
Insulin Secretion ◽  
Stimulation Index ◽  
Human Islets ◽  
Diabetic Patients ◽  
Second Phase ◽  
Biphasic Insulin ◽  
Biphasic Insulin Secretion ◽  
Normal Human ◽  
Second Phases

The biphasic pattern of glucose-induced insulin secretion is altered in type 2 diabetes. Impairment of the first phase is an early sign of β-cell dysfunction, but the underlying mechanisms are still unknown. Their identification through in vitro comparisons of islets from diabetic and control subjects requires characterization and quantification of the dynamics of insulin secretion by normal islets. When perifused normal human islets were stimulated with 15 mmol/l glucose (G15), the proinsulin/insulin ratio in secretory products rapidly and reversibly decreased (∼50%) and did not reaugment with time. Switching from prestimulatory G3 to G6–G30 induced biphasic insulin secretion with flat but sustained (2 h) second phases. Stimulation index reached 6.7- and 3.6-fold for the first and second phases induced by G10. Concentration dependency was similar for both phases, with half-maximal and maximal responses at G6.5 and G15, respectively. First-phase response to G15–G30 was diminished by short (30–60 min) prestimulation in G6 (vs. G3) and abolished by prestimulation in G8, whereas the second phase was unaffected. After 1–2 days of culture in G8 (instead of G5), islets were virtually unresponsive to G15. In both settings, a brief return to G3–G5 or transient omission of CaCl2 restored biphasic insulin secretion. Strikingly, tolbutamide and arginine evoked immediate insulin secretion in islets refractory to glucose. In conclusion, we quantitatively characterized the dynamics of glucose-induced insulin secretion in normal human islets and showed that slight elevation of prestimulatory glucose reversibly impairs the first phase, which supports the view that the similar impairment in type 2 diabetic patients might partially be a secondary phenomenon.

Dodecanedioic acid overcomes metabolic inflexibility in type 2 diabetic subjects

2006 ◽  
Vol 291 (5) ◽  
pp. E1051-E1058 ◽  
Author(s):  
Serenella Salinari ◽  
Alessandro Bertuzzi ◽  
Alberto Gandolfi ◽  
Aldo V. Greco ◽  
Antonino Scarfone ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Secretion ◽  
Central Compartment ◽  
Moderate Intensity ◽  
Second Phase ◽  
Nonesterified Fatty Acids ◽  
Glucose Ingestion ◽  
Dodecanedioic Acid ◽  
Type 2 Diabetic

Metabolically healthy skeletal muscle possesses the ability to switch easily between glucose and fat oxidation in response to homeostatic signals. In type 2 diabetes mellitus and obesity, the skeletal muscle shows a great reduction in this metabolic flexibility. A substrate like dodecanedioic acid (C-12), able to increase skeletal muscle glycogen stores via succinyl-CoA formation, might both postpone the fatigue and increase fatty acid utilization, since it does not affect insulin secretion. In healthy volunteers and in type 2 diabetic subjects, the effect of an oral C-12 load was compared with a glucose or water load during prolonged, moderate-intensity, physical exercise. C-12 metabolism was analyzed by a mathematical model. After C-12, diabetics were able to complete the 2 h of exercise. Nonesterified fatty acids increased both during and after the exercise in the C-12 session. C-12 oxidation provided 14% of total energy expenditure, and the sum of C-12 plus lipids oxidized after the C-12 meal was significantly greater than lipids oxidized after the glucose meal ( P < 0.025). The fraction of C-12 that entered the central compartment was 47% of that ingested. During the first phase of the exercise (∼60 min), the mean C-12 clearance from the central compartment toward tissues was 2.57 and 1.30 l/min during the second phase of the exercise. In conclusion, C-12 seems to be a suitable energy substrate during exercise, since it reduces muscle fatigue, is rapidly oxidized, and does not stimulate insulin secretion, which implies that lipolysis is not inhibited as reported after glucose ingestion.

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