Publication: ANTIDIABETIC ACTIVITY OF CATALPOL ON HIGH FAT DIET AND STREPTOZOTOCIN INDUCED TYPE-2 DIABETES MICE BY IMPROVING INSULIN SENSITIVITY AND MITOCHONDRIAL FUNCTION
Date
2023
Authors
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Publisher
International Medical University
Abstract
There is an urgent need in search of an insulin-sensitising agent exhibiting good safety, efficacy
and tolerability profile for the prevention and treatment of type-2 diabetes mellitus. Catalpol, an
iridoid glucoside, is the main bioactive component of Rehmannia glutinosa radix. Catalpol is
reported to possess anti-oxidant, neuro-protective and glucose-lowering effects. The work
described in this study aimed to examine the effects of catalpol in improving glycaemic control as
well as insulin sensitivity in both skeletal muscles and liver of type-2 diabetes mellitus mice. Male
C57BL/6N mice aged 5-6 weeks were placed on a high fat diet (60% kcal) for two weeks prior to
streptozotocin (50 mg/kg, i.p.) administration for three consecutive days. Group fed with normal
chow diet served as the normal control. Four groups of diabetic animals were administered orally
with saline, catalpol (100 mg/kg), catalpol (200 mg/kg) or metformin (200 mg/kg) once per day
for four consecutive weeks. Treatment of catalpol (200 mg/kg) significantly lowered fasting
plasma glucose compared to diabetic control (p < 0.01), along with attenuation of insulin resistance
by reducing HOMA-IR index. Catalpol improved insulin sensitivity in skeletal muscles through
activating AMPK/SIRT1/PGC-1a pathway. The downstream effect was observed in improved
mitochondrial respiration. Administration of catalpol increased the insulin sensitivity in liver by
up-regulating PPAR-g and suppressing the expression of gluconeogenic enzymes. Besides,
catalpol treatment improved lipid metabolism by regulating plasma adiponectin, plasma
triglycerides and liver triglycerides levels. Collectively, catalpol (200 mg/kg) exerted anti-diabetic
effects by improving glycaemic control, insulin sensitivity and mitochondrial function in skeletal
muscles. Besides, catalpol improved insulin sensitivity in liver and lipid metabolism.
Description
Keywords
Diabetes Mellitus, Type 2, Insulin, Glycemic Control, Insulin Resistance, Diet, High-Fat, Lipid Metabolism