Evidence for a circulating islet cell growth factor in insulin-resistant states

SN Flier, RN Kulkarni, CR Kahn - Proceedings of the …, 2001 - National Acad Sciences
SN Flier, RN Kulkarni, CR Kahn
Proceedings of the National Academy of Sciences, 2001National Acad Sciences
Insulin resistance is a feature of many common disorders including obesity and type 2
diabetes mellitus. In these disorders, the β-cells compensate for the insulin resistance for
long periods of time with an increase in secretory capacity, an increase in β-cell mass, or
both. To determine whether the β-cell response might relate to a circulating growth factor, we
have transplanted normal islets under the kidney capsule of normoglycemic insulin-resistant
mice with two different models of insulin resistance: lean mice that have a double …
Insulin resistance is a feature of many common disorders including obesity and type 2 diabetes mellitus. In these disorders, the β-cells compensate for the insulin resistance for long periods of time with an increase in secretory capacity, an increase in β-cell mass, or both. To determine whether the β-cell response might relate to a circulating growth factor, we have transplanted normal islets under the kidney capsule of normoglycemic insulin-resistant mice with two different models of insulin resistance: lean mice that have a double heterozygous deletion of the insulin receptor and insulin receptor substrate-1 (DH) or the obese, hyperglycemic ob/ob mice. In the grafts transplanted into both hosts, there was a marked increase in β-cell mitotic activity and islet mass that was comparable with that observed in the endogenous pancreas. By contrast, islets of the DH mouse transplanted into normal mice showed reduced mitotic index. These data suggest the insulin resistance is associated with a circulating islet cell growth factor that is independent of glucose and obesity.
National Acad Sciences