Central regulation of glucose metabolism in an insulin‐dependent and ‐independent manner

2021 ◽  
Vol 33 (4) ◽  
Author(s):  
Teppei Fujikawa
Keyword(s):  
Glucose Metabolism ◽  
Central Regulation ◽  
Independent Manner ◽  
Insulin Dependent

scholarly journals Role of cAMP in Double Switch of Glucagon Secretion

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 896
Author(s):  
Jan Zmazek ◽  
Vladimir Grubelnik ◽  
Rene Markovič ◽  
Marko Marhl
Keyword(s):  
Glucose Metabolism ◽  
Signaling Pathway ◽  
Cell Model ◽  
Dominant Role ◽  
Glucagon Secretion ◽  
Camp Signaling ◽  
Independent Manner ◽  
Metabolic Switch ◽  
Camp Signaling Pathway ◽  
Double Switch

Glucose metabolism plays a crucial role in modulating glucagon secretion in pancreatic alpha cells. However, the downstream effects of glucose metabolism and the activated signaling pathways influencing glucagon granule exocytosis are still obscure. We developed a computational alpha cell model, implementing metabolic pathways of glucose and free fatty acids (FFA) catabolism and an intrinsically activated cAMP signaling pathway. According to the model predictions, increased catabolic activity is able to suppress the cAMP signaling pathway, reducing exocytosis in a Ca2+-dependent and Ca2+ independent manner. The effect is synergistic to the pathway involving ATP-dependent closure of KATP channels and consequent reduction of Ca2+. We analyze the contribution of each pathway to glucagon secretion and show that both play decisive roles, providing a kind of “secure double switch”. The cAMP-driven signaling switch plays a dominant role, while the ATP-driven metabolic switch is less favored. The ratio is approximately 60:40, according to the most recent experimental evidence.

Glucose production, recycling, and gluconeogenesis in normals and diabetics: a mass isotopomer [U-13C]glucose study

1996 ◽  
Vol 270 (4) ◽  
pp. E709-E717 ◽  
Author(s):  
J. A. Tayek ◽  
J. Katz
Keyword(s):  
Glucose Metabolism ◽  
Plasma Glucose ◽  
Tricarboxylic Acid Cycle ◽  
Glucose Production ◽  
Insulin Dependent Diabetes Mellitus ◽  
Dependent Diabetes Mellitus ◽  
Glucose Turnover ◽  
Insulin Dependent ◽  
Gas Chromatography Mass Spectroscopy ◽  
Mass Isotopomer

Eight normal controls and nine non-insulin-dependent diabetes mellitus diabetics were, after an overnight fast, infused for 3 h with [6-3H]- and with [U-13C]glucose with six 13C carbons at rates from 0.03 to 0.15 mg.kg-1.min-1. Plasma glucose and lactate were assayed by gas chromatography-mass spectroscopy. Several parameters of glucose metabolism were calculated from the mass isotopomer distribution. Glucose production (GP) determined with [6-3H]- and [U-13C]glucose agreed closely. GP was 1.9 +/- 0.16 (range 1.3-2.5) mg.kg-1.min-1 in controls and 2.8 +/- 0.29 (1.7-4.5) mg.kg-1.min-1 in diabetics (P < 0.05). The correlation in diabetes between plasma glucose and GP (r = 0.911, P < 0.01) was close. Recycling of carbon (8 vs 7%) dilution by unlabeled carbon (2- vs 2.3-fold), and dilution via the tricarboxylic acid cycle (1.5-fold) were similar in controls and diabetics. Gluconeogenesis was 0.90 +/- 0.08 (0.5-1.3) mg.kg-1.min-1 in controls and 1.30 +/- 0.13 (0.8-1.9) mg.kg-1.min-1 in diabetics (P < 0.05). Gluconeogenesis contributions to GP were 46.6 +/- 4.0% (26-61%) in the controls and 48.8 +/- 5.7% (32-83%) in diabetics. We show that, using [U-13C]glucose infusion of 2-5% of glucose turnover (0.03-0.10 mg.kg-1.min-1), a large number of parameters of glucose metabolism may be determined in humans.

Effects of puberty and diabetes on metabolism of insulin-sensitive fuels

1994 ◽  
Vol 266 (6) ◽  
pp. E885-E891 ◽  
Author(s):  
S. Caprio ◽  
G. Cline ◽  
S. Boulware ◽  
C. Permanente ◽  
G. I. Shulman ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Lipid Oxidation ◽  
Insulin Infusion ◽  
Plasma Free Fatty Acid ◽  
Insulin Dependent Diabetes Mellitus ◽  
Dependent Diabetes Mellitus ◽  
Healthy Controls ◽  
Oxidation Rates ◽  
Acid Protein ◽  
Insulin Dependent

Insulin's ability to stimulate glucose metabolism is reduced during normal puberty; these changes are exaggerated in adolescents with insulin-dependent diabetes mellitus (IDDM). Because the effects of puberty and IDDM on the other actions of insulin have not been established, we studied leucine kinetics (using [1-13C]leucine) and fat metabolism during euglycemic hyperinsulinemia (20 mU.m2.min-1) for 3 h in eight healthy and nine IDDM (HbA1 14 +/- 2%) adolescents and six healthy young adult controls. IDDM subjects received overnight low-dose insulin infusion to normalize fasting glucose. Basal and steady-state insulin values (approximately 240 pM) during the study were similar in all three groups. Insulin-stimulated glucose metabolism was reduced by 40% in healthy adolescents vs. adults (P < 0.05) and by an additional 40% in poorly controlled IDDM (P < 0.05 vs, normal adolescents). Although basal glucose and lipid oxidation rates (measured by indirect calorimetry) were similar in all three groups, when insulin was infused, glucose oxidation increased and lipid oxidation decreased only in the two nondiabetic groups. Similarly, insulin significantly reduced plasma free fatty acid levels only in the nondiabetics. Basal leucine flux (an index of protein degradation) was similar in healthy controls but was markedly increased in IDDM adolescents. Despite similar increments in plasma insulin during the clamp, leucine flux remained higher in IDDM adolescents than in healthy controls. Basal leucine oxidation rates were also increased in IDDM subjects compared with nondiabetic groups and declined to a lesser extent during insulin infusion. We conclude that insulin resistance of puberty is selective for glucose metabolism, sparing amino acid/protein metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Overnight glucose metabolism in obese non-insulin-dependent diabetic patients and in healthy lean individuals

1994 ◽  
Vol 14 (3) ◽  
pp. 251-265 ◽  
Author(s):  
L. Tappy ◽  
K. Acheson ◽  
B. Curchod ◽  
Ph. Schneiter ◽  
S. Normand ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Diabetic Patients ◽  
Insulin Dependent ◽  
Insulin Dependent Diabetic
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