Can the glyoxylate pathway contribute to fat-induced hepatic insulin resistance?

Recent studies have shown that increased hepatic gluconeogenesis is the predominant contributor to fasting hyperglycemia - the hallmark of type 2 diabetes. Although it has been known for a long time that over-supply of fat is able to stimulate gluconeogenesis both in-vitro and in-vivo, neither the leading substrate nor the mechanism responsible for this phenomenon have been fully identified. Recent observations that the glyoxylate pathway may exist in animals has shed light on this question. The glyoxylate pathway is able to convert fatty acid into glucose but has been thought to be absent in animals. Although further evidence is needed, current available data does suggest a possible mechanism which, by integrating both glucose and lipid metabolism together rather than interpreting them separately, may explain the role of fatty acids in hepatic insulin resistance. This hypothesis is based on current understanding of insulin resistance and supported by many laboratory observations. (C) 2000 Harcourt Publishers Ltd.