Combining sitagliptin/metformin with a functional fiber delays diabetes progression in Zucker rats.

Abstract

Our primary objective was to determine whether administering the viscous and fermentable polysaccharide PolyGlycopleX (PGX) with metformin (MET) or sitagliptin/metformin (S/MET) reduces hyperglycemia in Zucker diabetic fatty (ZDF) rats more so than monotherapy of each. Glucose tolerance, adiposity, satiety hormones and mechanisms related to dipeptidyl peptidase 4 activity, gut microbiota and, hepatic and pancreatic histology were examined. Male ZDF rats (9-10 weeks of age) were randomized to: i) cellulose/vehicle (control, C); ii) PGX (5% wt/wt)/vehicle (PGX); iii) cellulose/metformin (200  mg/kg) (MET); iv) cellulose/S/MET (10  mg/kg+200  mg/kg) (S/MET); v) PGX (5%)+MET (200  mg/kg) (PGX+MET); vi) cellulose/sitagliptin/MET (5%)+(10  mg/kg+200  mg/kg) (PGX+S/MET) for 6 weeks. PGX+MET and PGX+S/MET reduced glycemia compared with C and singular treatments (P=0.001). Weekly fasted and fed blood glucose levels were lower in PGX+MET and PGX+S/MET compared with all other groups at weeks 4, 5, and 6 (P=0.001). HbA1c was lower in PGX+S/MET than C, MET, S/MET, and PGX at week 6 (P=0.001). Fat mass was lower and GLP1 was higher in PGX+S/MET compared with all other groups (P=0.001). β-cell mass was highest and islet degeneration lowest in PGX+S/MET. Hepatic lipidosis was significantly lower in PGX+S/MET compared with PGX or S/MET alone. When combined with PGX, both MET and S/MET markedly reduce glycemia; however, PGX+S/MET appears advantageous over PGX+MET in terms of increased β-cell mass and reduced adiposity. Both combination treatments attenuated diabetes in the obese Zucker rat.

• Authors: Raylene A Reimer, Gary J Grover, Lee Koetzner, Roland J Gahler, Michael R Lyon, Simon Wood
• Journal: The Journal of endocrinology (J Endocrinol) Vol. 220 Issue 3 Pg. 361-73 (Mar 2014) ISSN: 1479-6805 [Electronic] England
• PMID: 24389593 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Alginates
• Blood Glucose
• Drug Combinations
• Hypoglycemic Agents
• PolyGlycoplex
• Polysaccharides, Bacterial
• Pyrazines
• Triazoles
• Metformin
• Sitagliptin Phosphate

Topics

• Alginates (administration & dosage)
• Animals
• Blood Glucose (metabolism)
• Diabetes Mellitus, Type 2 (metabolism, pathology, prevention & control)
• Disease Progression
• Drug Combinations
• Drug Therapy, Combination
• Humans
• Hyperglycemia (drug therapy, metabolism, pathology)
• Hypoglycemic Agents (administration & dosage)
• Insulin-Secreting Cells (drug effects, metabolism)
• Male
• Metformin (administration & dosage)
• Polysaccharides, Bacterial (administration & dosage)
• Pyrazines (administration & dosage)
• Rats
• Rats, Zucker
• Sitagliptin Phosphate
• Triazoles (administration & dosage)