Continuous exposure of non-obese adult male rats to a soft-textured, readily absorbable diet induces insulin resistance and derangements in hepatic glucose and lipid metabolism.

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-hour restricted schedule over 14 weeks demonstrated glucose intolerance and insulin resistance with disruption of insulin signaling.

Objective: 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 non-obese male rats fed control pellets (CPs) or SPs on a 3-hour restricted schedule (10:00 to 13:00) for 4 and 9 weeks. At 11 weeks, we switched half of the insulin-resistant SP group to CPs (soft-to-control pellets [SCPs]) and after an additional 11 weeks, evaluated changes in glucose and lipid metabolism across the three groups.

Results: The glucose tolerance test results in the SP and CP rats did not differ at 4 or 9 weeks. 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 weeks compared with the controls (P < 0.05). At 22 weeks, the HOMA-IR, blood glucose levels at 30 minutes after initiating feeding, hepatic glucose metabolism, and lipid synthesis in the 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.