Metformin Can Attenuate Beta-Cell Hypersecretion-Implications for Treatment of Children with Obesity

In children with obesity, insulin hypersecretion is proposed to precede insulin resistance. We investigated if metformin could be used to attenuate insulin secretion from palmitate-treated isolated islets and its implication for children with obesity. Human islets were exposed to palmitate for 0.5 or 1 day, when metformin was introduced. After culture, glucose-stimulated insulin secretion (GSIS) was measured. Children with obesity, who had received metformin for over six months (n = 21, age 13.9 +/- 1.8), were retrospectively evaluated. Children were classified as either reducing or increasing based on the difference between AUC(0-120) of insulin during OGTT before and after metformin treatment. In human islets, GSIS increased after culture in palmitate for up to 1 day but declined with continued palmitate exposure. Whereas adding metformin after 1 day of palmitate exposure increased GSIS, adding metformin after 0.5 days reduced GSIS. In children with reducing insulin AUC(0-120) (n = 9), 2 h glucose and triglycerides decreased after metformin treatment, which was not observed in patients with increasing insulin AUC(0-120) (n = 12). In isolated islets, metformin attenuated insulin hypersecretion if introduced when islet secretory capacity was maintained. In children with obesity, improved glycemic and lipid levels were accompanied by reduced insulin levels during OGTT after metformin treatment.

Automated summary

The study investigated the effect of metformin on insulin secretion in isolated islets treated with palmitate and its implications for children with obesity. It was found that adding metformin after 1 day of palmitate exposure increased insulin secretion, while adding metformin after 0.5 days reduced insulin secretion. Additionally, metformin treatment in children with obesity improved glycemic and lipid levels and decreased insulin levels during OGTT.