Topic
Insulin
About: Insulin is a research topic. Over the lifetime, 124295 publications have been published within this topic receiving 5129734 citations. The topic is also known as: human insulin.
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TL;DR: In this paper, the AMPK-activated protein kinase (AMPK) is viewed as a fuel sensor for glucose and lipid metabolism, and a knockout mouse model was generated to better understand the physiological role of AMPK.
Abstract: AMP-activated protein kinase (AMPK) is viewed as a fuel sensor for glucose and lipid metabolism. To better understand the physiological role of AMPK, we generated a knockout mouse model in which the AMPKalpha2 catalytic subunit gene was inactivated. AMPKalpha2(-/-) mice presented high glucose levels in the fed period and during an oral glucose challenge associated with low insulin plasma levels. However, in isolated AMPKalpha2(-/-) pancreatic islets, glucose- and L-arginine-stimulated insulin secretion were not affected. AMPKalpha2(-/-) mice have reduced insulin-stimulated whole-body glucose utilization and muscle glycogen synthesis rates assessed in vivo by the hyperinsulinemic euglycemic clamp technique. Surprisingly, both parameters were not altered in mice expressing a dominant-negative mutant of AMPK in skeletal muscle. Furthermore, glucose transport was normal in incubated isolated AMPKalpha2(-/-) muscles. These data indicate that AMPKalpha2 in tissues other than skeletal muscles regulates insulin action. Concordantly, we found an increased daily urinary catecholamine excretion in AMPKalpha2(-/-) mice, suggesting altered function of the autonomic nervous system that could explain both the impaired insulin secretion and insulin sensitivity observed in vivo. Therefore, extramuscular AMPKalpha2 catalytic subunit is important for whole-body insulin action in vivo, probably through modulation of sympathetic nervous activity.
523 citations
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TL;DR: It is suggested that poor adherence to insulin treatment is the major factor that contributes to long-term poor glycaemic control and diabetic ketoacidosis in patients aged 10-20 years.
523 citations
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TL;DR: It is indicated that insulin is a physiological and dynamic modulator of plasma ghrelin and that insulinemia possibly mediates the effect of nutritional status on its concentration.
Abstract: Ghrelin is a novel gastric peptide which stimulates growth hormone and has orexigenic and adipogenic properties. Plasma ghrelin is influenced by nutritional status and is thought to play a role in regulating food intake and body weight. We examined the effect of infusing insulin (40 mU/m2/min) for 2 hours while maintaining euglycemia on plasma ghrelin in 8 subjects (5 M, 3 F) aged 46 ± 4 yrs (mean ± SEM). Plasma insulin increased from 78 ± 9 to 564± 23 pmol/L during and returned rapidly to basal values after stopping the insulin infusion. Plasma ghrelin decreased from 85 ± 28 to 61 ± 18 pmol/L (p < 0.01) by 90 minutes of and continued to be suppressed for 15 minutes after the insulin infusion was discontinued. Subsequently, plasma ghrelin rose rapidly to near-basal values (81 ± 23 pmol/L) within 60 minutes. The reciprocal relation between insulin and ghrelin was observed consistently in all subjects with the maximum insulin-induced suppression of ghrelin ranging from 19 to 64% (mean 32± 5) and occuring 90...
523 citations
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TL;DR: Following exercise, glucose transport and glycogen synthesis in skeletal muscle are enhanced due at least in part to an increase in insulin sensitivity, and it is suggested that this increase in diabetes sensitivity occurs predominantly in muscle fibers that are deglycogenated during exercise.
Abstract: Muscle glycogen stores are depleted during exercise and are rapidly repleted during the recovery period. To investigate the mechanism for this phenomenon, untrained male rats were run for 45 min on a motor-driven treadmill and the ability of their muscles to utilize glucose was then assessed during perfusion of their isolated hindquarters. Glucose utilization by the hindquarter was the same in exercised and control rats perfused in the absence of added insulin; however, when insulin (30-40,000 muU/ml) was added to the perfusate, glucose utilization was greater after exercise. Prior exercise lowered both, the concentration of insulin that half-maximally stimulated glucose utilization (exercise, 150 muU/ml; control, 480 muU/ml) and modestly increased its maximum effect. The increase in insulin sensitivity persisted for 4 h following exercise, but was not present after 24 h. The rate-limiting step in glucose utilization enhanced by prior exercise appeared to be glucose transport across the cell membrane, as in neither control nor exercised rats did free glucose accumulate in the muscle cell. Following exercise, the ability of insulin to stimulate the release of lactate into the perfusate was unaltered; however its ability to stimulate the incorporation of [(14)C]glucose into glycogen in certain muscles was enhanced. Thus at a concentration of 75 muU/ml insulin stimulated glycogen synthesis eightfold more in the fast-twitch red fibers of the red gastrocnemius than it did in the same muscle of nonexercised rats. In contrast, insulin only minimally increased glycogen synthesis in the fast-twitch white fibers of the gastrocnemius, which were not glycogen-depleted. The uptake of 2-deoxyglucose by these muscles followed a similar pattern suggesting that glucose transport was also differentially enhanced. Prior exercise did not enhance the ability of insulin to convert glycogen synthase from its glucose-6-phosphate-dependent (D) to its glucose-6-phosphate-independent (1) form. On the other hand, following exercise, insulin prevented a marked decrease in muscle glucose-6-phosphate, which could have diminished synthase activity in situ. The possibility that exercise enhanced the ability of insulin to convert glycogen synthase D to an intermediate form of the enzyme, more sensitive to glucose-6-phosphate, remains to be explored. These results suggest that following exercise, glucose transport and glycogen synthesis in skeletal muscle are enhanced due at least in part to an increase in insulin sensitivity. They also suggest that this increase in insulin sensitivity occurs predominantly in muscle fibers that are deglycogenated during exercise.
523 citations
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TL;DR: This work states that new understanding of the roles of other pancreatic and incretin hormones has led to a multi-hormonal view of glucose homeostasis.
Abstract: Insulin and glucagon are potent regulators of glucose metabolism. For
decades, we have viewed diabetes from a bi-hormonal perspective of glucose
regulation. This perspective is incomplete and inadequate in explaining some
of the difficulties that patients and practitioners face when attempting to
tightly control blood glucose concentrations. Intensively managing diabetes
with insulin is fraught with frustration and risk. Despite our best efforts,
glucose fluctuations are unpredictable, and hypoglycemia and weight gain are
common. These challenges may be a result of deficiencies or abnormalities in
other glucoregulatory hormones. New understanding of the roles of other
pancreatic and incretin hormones has led to a multi-hormonal view of glucose
homeostasis.
522 citations