Biology Question #1304

vanessa demelo, a 22 year old female from paris asks on March 4, 2003,

Why does insulin resistance induce weight gain? I don't understand because insulin is suposed to promote lipogenesis in normal patients. Then, if someone is insulin-resistant, insulin can't excercise its effect, lipogenesis is inhibited (lipolysis can occur) and he tends to lose weight...

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The answer

Dawn McArthur, SFU answered on March 9, 2003

Insulin resistance doesn't induce weight gain per se; it is a correlate of being overweight (in about 20% of those who are overweight; however, 80% of people with type 2 diabetes are overweight). Patients who are insulin resistant are usually hyperinsulinemic and hyperglycemic, and tend also to have other endocrine compensations, e.g., changes in glucagon, cortisol, etc., ... ultimately leading to a NET conversion of fuels for storage (glycogen, lipid).

Brian G. Topp, SFU Insulin Researcher answered on March 12, 2003

It is more likely that you have got that backwards; weight gain induces insulin resistance. Increasing or decreasing adiposity has been shown to increase or decrease insulin resistance respectively. However, experimental induction of insulin resistance does not necessarily lead to weight gain. Further, a good deal of lean people are in fact insulin resistant. The mechanism by which obesity leads to insulin resistance is much debated. The three leading proposals are 1) adipocytes are less insulin sensitivity than muscle cells, thus changing the ratio of muscle to fat will decrease insulin sensitivity, 2) lipids inhibit glucose metabolism and thus insulin action, and 3) intermediates of triglyceride storage in muscle and liver interfere with the insulin signaling cascade (lipotoxicity hypothesis).

However, it is possible that insulin resistance leads to weight gain. For example, assume that one develops insulin resistance at the muscle and/or liver. This leads to mild hyperglycemia which stimulates increased insulin secretion. Now keep in mind that the adipocytes maintain normal insulin action and are now being exposed to excessive insulin levels. Thus while muscle and liver are receiving relatively normal insulin action (decreased sensitivity offset by increased insulin levels) the adipocytes are being excessively stimulated and thus excessively storing lipids.

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