Continuous Exposure of Nonobese Adult Male Rats to a Soft-Textured, Readily Absorbable Diet Induces Insulin Resistance and Derangements in Hepatic Glucose and Lipid Metabolism.

Abstract

Background: Type 2 diabetes (T2D) is characterized by insulin resistance and defective insulin secretion. Previously, we found that rats fed soft pellets (SPs) on a 3-h restricted schedule over 14 wk demonstrated glucose intolerance and insulin resistance with disruption of insulin signaling.

Objectives: This study aims to determine 1) the time required for an SP diet to induce insulin resistance, and 2) whether the metabolic derangements in rats fed SPs can be reversed by changing to a standard control diet.

Methods: We performed glucose tolerance tests and calculated the homeostasis model assessment of insulin resistance (HOMA-IR) to evaluate the insulinemic response to glucose and assess insulin resistance in nonobese male rats fed control pellets (CPs) or SPs on a 3-h restricted schedule (10:00-13:00) for 4 and 9 wk. At 11 wk, we switched half of the insulin-resistant SP group to CPs [soft-to-control pellets (SCPs)] and after an additional 11 wk evaluated changes in glucose and lipid metabolism across the 3 groups.

Results: The glucose tolerance test results in the SP and CP rats did not differ at 4 or 9 wk. The insulin levels in the SP group were higher than in the CP group at both time points (P < 0.05). The HOMA-IR was significantly higher in the SP rats at 9 wk compared with the controls (P < 0.05). At 22 wk, the HOMA-IR, blood glucose levels at 30 min after initiating feeding, hepatic glucose metabolism, and lipid synthesis in rats fed SPs continuously were significantly greater than in those fed CPs (P < 0.05); however, these values in the SCP rats did not differ from those in the CP rats.

Conclusions: A continuous diet of soft-textured, readily absorbable food may be an important and reversible underlying driver in T2D pathogenesis.