In health, the blood glucose concentration remains remarkably stable even after prolonged fasting (Figure 1). After an overnight fast, basal insulin concentrations are relatively low, and insufficient to stimulate glucose uptake by muscle and fat. Under these conditions glucose uptake is primarily by insulin-independent tissues such as brain, red blood cells, and the kidney. With fasting, insulin-dependent tissues rely primarily on free fatty acids for energy. These free fatty acids are derived from breakdown of fat stores (triglyceride). Blood glucose remains constant because the liver releases glucose derived initially from glycogenoly-sis—and, with time, increasingly from gluconeogenesis—at a rate that matches that of glucose uptake.
The basal rate of insulin is sufficient to constrain the rate of hepatic glucose release to match that of glucose uptake. In the absence of this basal insulin, the rate of hepatic glucose release would be much greater and the blood glucose concentration would increase. The basal rate of insulin is also sufficient to constrain levels of lipolysis to provide sufficient FFA for oxidation by muscle and fat. In the complete absence of insulin, lipolysis would occur at much higher rates and excessive FFA would be converted to ketones in the liver, resulting in diabetic ketoacidosis (18).
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