Mouse without SCD resists diabetes 2/9/03. By the University of Wisconsin-Madison An engineered mouse, already known to be immune to the weight gain ramifications of a high-calorie, high-fat diet, now seems able to resist the onset of diabetes.

The mouse, stripped of a gene known as SCD-1, is apparently impervious to the negative effects of the type of diet that, for many people, has significant health and social consequences.

The new finding is important because it provides critical genetic and biochemical clues to diet, obesity and the onset of type 2 diabetes.

The research, led by Dr James Ntambi at the University of Wisconsin-Madison, was published in the 1 September 2003 online edition of the Proceedings of the National Academy of Sciences.

The new finding is important because it provides critical genetic and biochemical clues to diet, obesity and the onset of type 2 diabetes.

Type 2 diabetes, which accounts for about 90 per cent of the incidence of diabetes, is a chronic disease caused by a problem in the way the body makes or uses insulin. Insulin is a hormone secreted by the pancreas that, under healthy circumstances, plays an essential role in moving glucose from blood to cells where the sugar's energy is expended.

In many instances, obesity and diabetes go hand in hand. Between 75 and 80 per cent of people with type 2 diabetes are obese, although the disease can also develop in lean people, especially the elderly.

The discovery of a gene that seems to exercise significant influence over both weight gain and glucose regulation promises a potentially significant window into both conditions and their relationship. The gene makes an enzyme called SCD. It affects the production of fatty acids, and because humans have SCD-1 equivalents, the new finding helps explain why some people, who may lack the gene, remain lean and diabetes free, despite a rich, fatty diet.

"We are beginning to suspect that obese individuals have increased expression of this enzyme," says Ntambi. "If you reduce expression of this enzyme, you reduce fat expression in muscle."

This new insight into the gene and its influence could herald the development of new drugs to prevent both diabetes and obesity as it may help scientists zero in on the underlying problems that lead to both conditions.

In the engineered mice, the Wisconsin team observed that muscle cells were more sensitive to insulin, enabling the cells to absorb glucose and avoid hyperglycaemia. Elevated levels of glucose in the blood prompt the pancreas to produce more insulin, which tends to make cells even more resistant to the critical hormone.

"In this animal, there is increased insulin signalling or sensitivity," Ntambi explains. "When insulin binds to the cell's insulin receptor, it triggers a cascade of events that enables the animal to successfully regulate levels of blood sugar.”

"There are lots of steps involved in the process, and in the case of type 2 diabetes things go wrong in some of those events," Ntambi says. "What we found in these animals is that the insulin signalling steps in muscle are all enhanced, despite low levels of insulin in plasma. We don't see a defect yet."

Adapted from a press release by the University of Wisconsin-Madison.

Further reading

Rahman SM et al. Stearoyl-CoA desaturase 1 deficiency elevates insulin-signaling components and down-regulates protein-tyrosine phosphatase 1B in muscle. Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):11110-5. Full text

Links

Dr James Ntambi research page