In the overnight fasted state, the liver has —50 g of glucose stored as glycogen (2). Glycogen breakdown to glucose-6-phosphate in the liver is stimulated by glucagon, epinephrine, growth hormone, and Cortisol (Table I) (I). The concentration of these hormones increases with duration of fasting. After —40 hours of fasting, the liver glycogen stores are largely depleted and gluconeogenesis becomes the predominant source of hepatic glucose release. Gluconeogenesis is the synthesis of glucose-6-phosphate from three carbon precursors, such as glycerol, lactate, and amino acids. Both gluconeogenesis and glycogenosis to generate glucose-6-phosphate occur in almost all tissues. However, glucose-6-phosphate cannot be released from the cell into the circulation until the phosphate is removed. The enzyme required to facilitate this (glucose-6-phosphatase) is abundant in liver but not present in fat or muscle. Therefore, in the fasting state almost all glucose released into the blood arises from the liver (so-called hepatic glucose release). In health, after an overnight fast the liver releases glucose at —2 mg/ kg/min, which approximates the rate of glucose uptake (3). In patients with diabetes, fasting hyperglycemia is due to increased hepatic glucose release. The fasting blood glucose concentration is correlated with the rate of hepatic glucose release, and so the higher the rate of hepatic glucose release the higher the blood glucose concentration (4).
It follows that to decrease the fasting blood glucose concentration to normal in patients with diabetes it is necessary to decrease the rate of hepatic glucose release to —2 mg/kg/min.
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Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...