Plasma Insulin is Required for the Increase in Plasma ANGPTL8 in Response to Nutrient Ingestion.

BACKGROUND: Plasma levels of ANGPTL8 are regulated by feeding, and they increase following glucose ingestion. Because both plasma glucose and insulin increase following food ingestion, we aimed to determine whether the increase in plasma insulin, glucose or both are responsible for the increase in ANGPTL8 levels.

METHODS: ANGPTL8 levels were measured in 30 subjects, 14 with impaired fasting glucose (IFG) and 16 with normal fasting glucose (NFG) received 75g glucose (oral Glucose tolerance test) OGTT, multistep euglycemic hyperinsulinemic clamp and hyperglycemic clamp with pancreatic clamp.

RESULTS: Subjects with IFG had significantly higher ANGPTL8 than NGT during the fasting state (p<0.05). During the OGTT, plasma ANGPTL8 concentration increased by 62% above the fasting level (p<0.0001), and the increase above fasting in ANGPTL8 levels was similar in NFG and IFG individuals. During the multistep insulin clamp, there was a dose-dependent increase in plasma ANGPTL8 concentration. During the 2-step hyperglycemic clamp, the rise in plasma glucose concentration failed to cause any change in the plasma ANGPTL8 concentration from baseline.

CONCLUSION: In response to nutrient ingestion, ANGPTL8 level was increased due to increased plasma insulin concentration, not the rise in plasma glucose. The incremental increase above baseline in plasma ANGLPTL8 during OGTT was comparable between people with normal glucose tolerance and impaired fasting glucose. This article is protected by copyright. All rights reserved.