Short-term administration of high dose dexamethasone can induce maximum insulin resistance in Wistar albino rats

Nagendranayak IM; Rajasekhar Chinta; Kokila B Nagaraju; Raghu Jetti

Nagendranayak IM Department of pharmacology, Mount-Zion Medical College, Adoor, Kerala, India
Rajasekhar Chinta Manipal Academy of Higher Education
Kokila B Nagaraju Department of Pharmacology, Melaka Manipal Medical College, Manipal Academy of Higher Education, Karnataka, India
Raghu Jetti Department of Basic Medical Sciences, College of Applied Medical Sciences, King Khalid University, Guraiger, Abha, Kingdom of Saudi Arabia

Abstract

Summery

Background: Long term administration of dexamethasone induces adverse effects such as muscle catabolism, hyperplasia, increased adiposity, and insulin resistance (IR). In view of these data, many authors tried to induce IR with different individual dose ranges with varied induction period. In this study, dexamethasone was used to find the dose to induce maximum insulin resistance in rodents. Methods: A sum of 42 healthy male Wistar albino rats were categorized into six groups of dexamethasone treatment and one control group (n=6/group). In a six-day study period, all treatment groups received respective graded doses of dexamethasone starting from low- (0.5mg/kg and 1mg/kg), intermediate- (2mg/kg and 4mg/kg) and high-dose (8mg/kg and 16mg/kg). Results: Graded doses of dexamethasone treatment for six days produced hyperglycemia and hyperinsulinemia in a dose-dependent manner and the maximum effect was noted with high doses of dexamethasone compared to intermediate and low (p<0.05). The profound reduction in insulin sensitivity was caused by high-doses of dexamethasone treatment evidenced by sustained elevation of homeostatic model assessment of insulin resistance (HOMA-IR) which was strongly associated with declined homeostatic model assessment of insulin sensitivity (HOMA-IS), The peripheral sensitivity indices, Gutt and Matsuda, were markedly elevated in high dexamethasone groups compared to intermediate- and low-dose groups (p<0.05). Serum lipids and creatinine (p<0.05), whereas high density lipoprotein cholesterol (HDL-CH) was markedly reduced and resulted in the subsequent rise in atherogenic index (AGI) (p<0.05). Moderate to severe glycosuria and ketonuria were noted in intermediate- and high-dose treatment groups only. However, there is no significant difference in metabolic effects between 8mg/kg and 16mg/kg treatments (p>0.05). Conclusion: Administration of 8mg/kg dexamethasone for six days would be sufficient for the induction of maximum insulin resistance in Wistar albino rats.

Keywords: HOMA, insulin resistance, hyperglycemia, hyperinsulinemia, metabolic effects