Hyperinsulinemia: a Cause of Obesity?

Abstract

Purpose of review: This perspective is motivated by the need to question dogma that does not work: that the problem is insulin resistance (IR). We highlight the need to investigate potential environmental obesogens and toxins.

Recent findings: The prequel to severe metabolic disease includes three interacting components that are abnormal: (a) IR, (b) elevated lipids and (c) elevated basal insulin (HI). HI is more common than IR and is a significant independent predictor of diabetes. We hypothesize that (1) the initiating defect is HI that increases nutrient consumption and hyperlipidemia (HL); (2) the cause of HI may include food additives, environmental obesogens or toxins that have entered our food supply since 1980; and (3) HI is sustained by HL derived from increased adipose mass and leads to IR. We suggest that HI and HL are early indicators of metabolic dysfunction and treating and reversing these abnormalities may prevent the development of more serious metabolic disease.

Keywords: Energy efficiency; Hyperinsulinemia; Hyperlipidemia; Insulin resistance; ROS; Redox.

Fig. 1

Chronic exposure to excess glucose and oleate increases proinsulin secretion. a INS-1 cells cultured in 4 mM glucose have lower proinsulin secretion at both basal (2 mM) and stimulatory (8 mM) glucose compared to those cultured at 11 mM glucose and 0.15 mM oleate for 48 h. b 4G cells have a lower ratio of secreted PI/insulin ratio compared to cells cultured at 11 mM glucose and 0.15 mM oleate (n = 6 independent experiments). Data are mean ± SEM. *p < 0.05 versus control (4G cells). Data are mean ± SEM. *p < 0.05 versus respective control (Student’s t test)