Hepatic sensitivity to insulin: effects of sulfonylurea drugs

Article Abstract:

Non-insulin-dependent diabetes mellitus (NIDDM) is characterized by abnormally high fasting blood glucose levels. It appears to be caused, in part, by decreased insulin sensitivity in the liver, which leads to increased glucose production, and by decreased insulin sensitivity in various tissues, which leads to reduced glucose uptake. Studies have shown that fasting blood glucose levels and glucose production by the liver are closely related. Treatments that could increase the liver's sensitivity to insulin during fasting could be very beneficial in controlling glucose levels. This review examined data concerning the effects of sulfonylurea agents on insulin-mediated glucose metabolism in the liver. Early studies on animal models showed that these drugs could suppress glucose production by the liver, and further animal studies revealed the possible mechanisms by which this might occur. Some studies found that sulfonylureas inhibit the breakdown of liver glycogen (storage form of glucose) and stimulate the liver to produce glycogen. Other studies showed that these drugs inhibit liver gluconeogenesis (producing glucose from fat and protein sources) and act on the insulin receptors on liver cells. Research has also been performed with patients who have NIDDM. Initial studies showed that sulfonylureas are useful in lowering blood glucose levels, but the mechanism by which they work was not clear and remains so. Further studies in patients found that these drugs decreased glucose production in the liver, but it is not clear if this is a direct result of the drug's effects on the liver or if it is an indirect result of increased insulin secretion. More recent research has indicated that both direct and indirect mechanisms are involved in suppressing liver glucose production. They suggest that although a certain amount of insulin secretion is required for sulfonylurea agents to be effective in reducing glucose production, the diminished production can not solely be explained by the increase in insulin. Further studies should clarify the effects these drugs have on the liver. (Consumer Summary produced by Reliance Medical Information, Inc.)

Liver cells, Hepatocytes, Sulfonylurea compounds, Sulfonylureas

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Rationale for the association of sulfonylurea and insulin

Article Abstract:

Non-insulin-dependent diabetes mellitus (NIDDM) is characterized by hyperglycemia, or high blood glucose levels. People with NIDDM are at much higher risk for developing vascular diseases such as heart disease and retinopathy. Proper treatment is needed to prevent these complications and requires an understanding of the causes of NIDDM. It is generally assumed that NIDDM results from various abnormalities that affect glucose metabolism. These include decreased or abnormal functioning of the pancreatic beta cells, which release the hormones insulin and glucagon, reduced insulin action on the liver, and reduced insulin action on tissues. Blood insulin levels may be normal or elevated in NIDDM, but in response to glucose stimulation, insulin does not increase adequately. Further, during fasting (not eating), adequate insulin levels to not result in lowering blood glucose levels, indicating a poor insulin response in tissues. Sulfonylurea agents are a group of drugs used to treat NIDDM and have been shown to be effective in maintaining excellent glycemic (blood glucose) control. They appear to work by increasing insulin secretion by the pancreatic beta cells and possibly increasing sensitivity to insulin. Insulin therapy can also be effective in treating NIDDM patients, enabling them to maintain excellent glycemic control. However, it is not used very often in NIDDM because of the severe side effects associated with it. Combined therapy with sulfonylurea agents and insulin has been suggested. It is thought that the two drugs may complement and enhance the effects of each other. Smaller amount of insulin could be used, lessening the risks of side effects. Results of studies using combined therapy have shown promising results. Such therapy appears most useful in treating patients who do not respond to sulfonylurea therapy alone or who do not obtain good glycemic control with insulin. Further studies are required to identify patients who might benefit from combined therapy and what the most appropriate drug combination might be. (Consumer Summary produced by Reliance Medical Information, Inc.)

Cases, Insulin, Drug synergism, Gliclazide

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Effects of chronic alcohol intake on carbohydrate and lipid metabolism in subjects with type II (non-insulin-dependent) diabetes

Article Abstract:

Insulin is a hormone made and released by the beta cells of the pancreas. Insulin is released into the blood following a meal, when blood glucose levels are high. Glucose is then transported by insulin from the blood to the body cells for fuel, and to the liver, where the glucose is converted to glycogen (the storage form of glucose). Between meals, when blood glucose levels drop, the liver releases glucose back into the blood in order to maintain relatively constant levels of blood sugar. In diabetes, the production of insulin, or its utilization by body cells, is impaired. This leads to elevated levels of glucose in the blood. Chronic consumption of alcohol by non-diabetic individuals has been reported to produce physiological changes similar to those observed in diabetes. Alcohol inhibits the secretion of insulin from the pancreas and interferes with the biological activity of insulin. This means that less glucose is removed from the blood, and more glucose is excreted in the urine. The effect of chronic alcohol consumption on carbohydrate and lipid metabolism was evaluated in patients with and without non-insulin-dependent diabetes mellitus (NIDDM, or type II diabetes). There were 46 patients who habitually drank alcohol and had NIDDM (NIDDM-B group, mean age of 67 years), 35 who did not drink alcohol but had NIDDM (NIDDM group, mean age of 65 years), and 40 normal control subjects (mean age of 66 years). The NIDDM-B group had higher fasting and postprandial (after a meal) blood levels of glucose, and higher blood levels of free fatty acids than the NIDDM group and the control group. When alcohol consumption was stopped, the metabolic effects of the alcohol were reversed within three days. It is concluded that chronic alcohol consumption impairs metabolic function in patients with NIDDM, who already have compromised mechanisms for metabolizing carbohydrates. (Consumer Summary produced by Reliance Medical Information, Inc.)

Diabetics, Alcohol, Ethanol, Carbohydrate metabolism, Alcohol use

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