Physiologic action of glucagon on liver glucose metabolism

Diabetes, Obesity and Metabolism - Tập 13 Số s1 - Trang 118-125 - 2011
Christopher J. Ramnanan1, Dale S. Edgerton1, Guillaume Kraft1, Alan D. Cherrington1
1Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232-0615, USA

Tóm tắt

Glucagon is a primary regulator of hepatic glucose production (HGP) in vivo during fasting, exercise and hypoglycaemia. Glucagon also plays a role in limiting hepatic glucose uptake and producing the hyperglycaemic phenotype associated with insulin deficiency and insulin resistance. In response to a physiological rise in glucagon, HGP is rapidly stimulated. This increase in HGP is entirely attributable to an enhancement of glycogenolysis, with little to no acute effect on gluconeogenesis. This dramatic rise in glycogenolysis in response to hyperglucagonemia wanes with time. A component of this waning effect is known to be independent of hyperglycemia, though the molecular basis for this tachyphylaxis is not fully understood. In the overnight fasted state, the presence of basal glucagon secretion is essential in countering the suppressive effects of basal insulin, resulting in the maintenance of appropriate levels of glycogenolysis, fasting HGP and blood glucose. The enhancement of glycogenolysis in response to elevated glucagon is critical in the life‐preserving counterregulatory response to hypoglycaemia, as well as a key factor in providing adequate circulating glucose for working muscle during exercise. Finally, glucagon has a key role in promoting the catabolic consequences associated with states of deficient insulin action, which supports the therapeutic potential in developing glucagon receptor antagonists or inhibitors of glucagon secretion.

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Thông tin xuất bản

Diabetes, Obesity and Metabolism

Tập 13 Số s1

118-125

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