Potentiation of incretin hormones and modulation of metabolic enzymes as possible mechanisms behind the insulin sensitizing effects of cabbage-metformin treatment

Abstract

In our study, we treated high fructose diet-induced insulin resistance in rats with any of metformin, cabbage (80%w/w) or combined metformin and cabbage (MetCabb), and observed the activities of glycolysis and gluconeogenesis regulatory enzymes, incretin hormones and other hormones affecting glucose homeostasis. Comparisons were made with normoglycemic noninsulin resistance rats (control) and insulin-resistant untreated rats (INres). Baseline analysis showing elevated fasting blood sugar (>250 mg/dl), insulin (>25 µIU/ml) and HOMA-IR (>10) satisfied the criteria for recruitment into the insulin-resistant groups. Treatment lasted for 12 weeks. HOMA-IR values significantly (P < 0.05) decreased from 24.7 to 5.5 and 10.6 respectively with MetCabb treatment. MetCabb normalized HOMA-IR values and mean β-cell responsiveness of the INres. Cabbage and metCabb normalized the leptin levels relative to control. The mean fasting blood sugar, insulin, and c-peptide levels with MetCabb treatment reverted to control levels. We found a strong positive linear correlation between the glucagon levels (r = 0.9145) and increasing HOMA-IR values while both incretin hormones; GLP-1 and GIP negatively regressed (r = -0.8084 and -0.8488). MetCab treatment produced comparable values of GLP-1 and GIP to the control. A strong positive correlation was found between the HOMA-IR values and the PEPCK (r = 0.9065), F-1,6-BPase (r = 0.7951), and G-6-Pase (r = 0.7893). The hexokinase (r = -0.807), PFK (r = -0.9151), and PK (r = -0.7448) levels regressed as HOMA-IR values increased. The glycolytic and gluconeogenic enzymes except PEPCK reverted to control levels with MetCabb treatment. Combination of metformin and cabbage was more effective than individual treatments.