Diabetes and the Alpha Cell

Diabetes and the Alpha Cell

John E Gerich
US Endocrine Disease 2006 Issue 2
Published: October 2008
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Despite wide variations throughout the course of a day in both the body’s glucose demand (e.g. during exercise) and the glucose supply (e.g. following meal ingestion), plasma glucose concentrations rarely exceed 160mg/dL or fall below 60mg/dL.1 This exquisite regulation is dependent on the body’s ability to balance the movement of glucose into and out of the plasma. Although numerous factors contribute to this process (e.g. the release of hormones and the body’s sensitivity to them, neurohumoral mechanisms, and the supply of substrates), the major regulators on a moment-to-moment basis are insulin, glucagon, and catecholamines.2

In the post-absorptive period (overnight fast), a quasisteady state exists in which the rate of glucose release into plasma approximates its removal. Under these conditions, most of glucose removal from plasma is independent of insulin (i.e. it is largely determined by obligatory tissue demands). For example, glucose uptake by the brain, the formed elements of the blood, the renal medulla, and the intestine, all of which do not require insulin, account for 70–80% of glucose disposal.1

In contrast, the release of glucose into the circulation is mainly regulated by insulin, glucagon, and catecholamines. The liver and kidneys account for ~80% and ~20% of glucose release, respectively.3 Insulin restrains hepatic and renal glucose release, while glucagon and catecholamines promote glucose release by the liver and kidneys, respectively. It is thus clear that in the post-absorptive period, the release of glucose into the circulation is largely the result of the actions of insulin and glucagon and is the primary means by which plasma glucose concentrations are regulated.

In the postprandial period (e.g. the four- to six-hour period following meal ingestion), insulin-mediated tissue uptake of glucose assumes a more important role than in the post-absorptive period; however, regulation of glucose release into the circulation is still the most important factor.4 Normally after meal ingestion, glucose release by the liver from endogenous sources (glycogenolysis and gluconeogenesis) is suppressed, while glucose release into the circulation from carbohydrates in the meal is largely dependent on first-pass hepatic extraction. In addition, the liver takes up glucose from the systemic circulation, such that after meal ingestion, total glucose uptake by the liver is approximately the same as muscle glucose uptake.

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