The removal of a receptor called ALK7 has the effect of increased insulin release and decreased weight gain, according to two recent complementary Swedish studies. The results could lead to novel ways to treat diabetes and obesity.
Diabetes is characterized by an inability to produce insulin (type 1), or insulin resistance and reduced insulin sensitivity (type 2). The disease, which is estimated to be present in upwards of 30 million Americans, has also been closely linked to obesity.
The studies in question were conducted on “mutant” mice that lacked the ALK7 receptor. The results showed an abnormally high level of insulin release, as well as a decreased level of weight gain on a high-caloric diet. The high insulin release levels, while promising in theory (for diabetics with the inability to produce normal levels of insulin), showed problems for the mice in the long-term, such as liver disease and reduced insulin sensitivity (this seems to indicate that by perhaps treating type 1 diabetes by increasing insulin production, type 2 diabetes can develop in the future).
More specifically, the study notes that “mutant mice lacking ALK7 showed normal pancreas organogenesis but developed an age-dependent syndrome involving progressive hyperinsulinemia, reduced insulin sensitivity, liver steatosis, impaired glucose tolerance, and islet enlargement. Hyperinsulinemia preceded the development of any other defect, indicating that this may be one primary consequence of the lack of ALK7. In agreement with this, mutant islets showed enhanced insulin secretion under sustained glucose stimulation, indicating that ALK7 negatively regulates glucose-stimulated insulin release in beta-cells.” Liver steatosis is characterized by an enlargement of the liver and a high buildup of fat. Hyperinsulinemia is often a present in type 2 diabetics and is characterized by excess insulin in the blood.
There was also a profound effect on fat accumulation observed in the mutant mice. “Mutant mice lacking ALK7 also showed reduced fat accumulation and partial resistance to diet-induced obesity,” according to the second study. It was also found in this study that “another growth factor called GDF3 could also signal via the ALK7 receptor, and that mice lacking GDF3 showed similar defects in fat deposition and weight gain as the ALK7 mutants.” Given the same level of high-fat food intake as non-mutant mice, and the observed gaining of less weight, “show that lack of ALK7 or GDF3 improves energy balance in the body under regimes of high caloric intake,” according to study author Dr. Carlos Ibanez.
The results of these two studies could have far-reaching implications, in no small part due to the fact that diabetes and obesity are already very closely linked. The discovery that the ALK7, or lack thereof, is potentially responsible for increased pancreatic insulin secretion, in conjunction with less weight gain, is very important. High levels of weight gain (obesity), often lead to insulin resistance and diabetes, so these studies provide the possibility of attacking and treating diabetes from two fronts.
Source: Defeat Diabetes Foundation: Ibanez, Carlos. Bertolino, Phillipe. et al. PNAS online. “Activin B receptor ALK7 is a negative regulator of pancreatic â-cell function.” May 2008. Ibanez, Carlos. Bertolino, Phillipe. et al. PNAS online. “Growth/differentiation factor 3 signals through ALK7 and regulates accumulation of adipose tissue and diet-induced obesity.” May 2008. Sternudd, Katarina. PNAS press release. May 2008