A new hormone has been identified that links obesity to type 2 diabetes. It has been called resistin (for “resistance to insulin”), and, although first identified in mice, it has also now been found in humans. Its US discoverers believe that it goes some of the way to explaining how obesity predisposes people to diabetes (Nature 2001;409:307-12).
Type 2 diabetes has long been observed to be associated with obesity. Insulin resistance is the hallmark of type 2 diabetes and is manifested all over the body. In addition, thiazolidinediones, the new class of antidiabetic drugs that lower insulin resistance are mediated by PPARg receptors, which are particularly abundant in fat cells.
From these two facts, scientists have hypothesised that it is the body's fat cells that trigger insulin resistance around the rest of the body. Now Dr Mitchell Lazar and his colleagues at the Pennsylvania School of Medicine claim they have identified a fat cell protein that may be responsible for this.
Dr Lazar, director of the Penn Diabetes Center, assumed that thiazolidinediones may work via PPARg receptors to switch on or off a fat cell specific gene that is involved in insulin mediated signalling pathways.
He and his team treated cultured fat cells with thiazolidinediones, and in doing so identified a new messenger RNA (mRNA) that was expressed only in adipose tissue and is suppressed by thiazolidinediones. This new mRNA encodes for a protein which is produced in plentiful supply by the adipose tissue of obese rodents.
Furthermore, secretion of the new protein from fat cells into the blood stream was reduced when these mice were treated with thiazolidinediones. “The secreted molecule resembled nothing we'd seen before, and because it has a cellular export signal, we identified it as a hormone,” explained Dr Lazar. The researchers went on to show that the hormone, which they named resistin, is also found to circulate in high levels in diabetic mice.
The next step is to produce a resistin knock-out mouse to confirm that resistin is critical in the development of diabetes, and also to administer purified resistin to normal mice to see if this reduces their ability to handle glucose.
Figure.
As fat cells (adipocytes) store more fat molecules, they release several products that can modify the body's sensitivity to insulin, such as free fatty acids and tumour necrosis factor a (TNF-a), which cause insulin resistance. A newly identified protein, resistin, which is secreted by adipocytes, causes insulin resistance. Thiazolidinedione drugs, which are used to treat type 2 diabetes, may work through suppressing the expression of resistin by adipocytes.