Enhanced Glucose Tolerance and Pancreatic Beta Cell Function by Low Dose Aspirin in Hyperglycemic Insulin-Resistant Type 2 Diabetic Goto-Kakizaki (GK) Rats

Abstract

Background/Aim: Type 2 diabetes is the most common metabolic disorder, characterized by insulin resistance and pancreatic islet beta-cell failure. The most common complications associated with type 2 diabetes are hyperinsulinemia, hyperglycemia, hyperlipidemia, increased inflammatory and reduced insulin response. Aspirin (ASA) and other non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with the prevention of diabetes, obesity and related cardiovascular disorders. Aspirin has been used in many clinical and experimental trials for the prevention of diabetes and associated complications. Methods: In this study, five month old Goto-Kakizaki (GK) rats, which showed signs of mild hyperglycemia (fasting blood glucose 80-95 mg/dl vs 55-60 mg/dl Wistar control rats) were used. Two subgroups of GK and Wistar control rats were injected intraperitoneally with 100 mg aspirin/kg body weight/ day for 5 weeks. Animals were sacrificed and blood and tissues were collected after performing glucose tolerance (2 h post 2g IP glucose ingestion) tests in experimental and control groups. Results: Aspirin caused a moderate decrease in hyperglycemia. However, we observed a significant improvement in glucose tolerance after ASA treatment in GK rats compared to the nondiabetic Wistar rats. Also, the ASA treated GK rats exhibited a significant decrease in insulinemia. ASA treatment also caused a marked reduction in the pro-inflammatory prostaglandin, PGE2, which was significantly higher in GK rats. On the other hand, no significant organ toxicity was observed after ASA treatment at this dose and time period. However, the total cholesterol and lipoprotein levels were significantly increased in GK rats, which decreased after ASA treatment. Immunofluorescence staining for insulin/glucagon secreting pancreatic cells showed improved beta-cell structural and functional integrity in ASA-treated rats which was also confirmed by SDS-PAGE and Western blot analysis. Conclusion: The improved glucose tolerance in ASA-treated GK rats may be associated with increased insulin responses due to the anti-inflammatory properties of ASA and enhanced nitric oxide (NO) level which facilitated insulin signaling and energy utilization in target tissues. These results may have implications in determining the therapeutic use of ASA in insulin-resistant type 2 diabetes.

Insulin augmentation and glucagon inhibition in cinnamon treated diabetic rats

“…CN may possess the ability to enhance leptin sensitivity and correct leptin resistance (Kim et al, 2006). The histological and ultrastructure damage reported in pancreas tissue as a result of AL injection come in agreement with those of Kumar and Clark (2005) who showed that islets containing residual β cells and it supports the possibility of a specific, immunologically mediated destruction of β cells as the cause of type 1 diabetes mellitus (Anderson, 1985); causing decrease in insulin expression and increase in glucagon expression (Amiri et al, 2015). There was heavy inflammatory infiltration in and around the islet (Eliakim-Ikechukwu&Obri, 2009).…”

Prostaglandin F2α Facilitates Hepatic Glucose Production Through CaMKIIγ/p38/FOXO1 Signaling Pathway in Fasting and Obesity

“…Here, we found that FP silencing significantly improved insulin sensitivity in ob/ob mice, probably because of suppression of hepatic gluconeogenesis. Indeed, aspirin administration, which reduces PG production by inhibiting cyclooxygenase activity, dramatically reduces fasting plasma glucose in patients with type 2 diabetes and diabetic rats (40,41). Taken together, increased PGF 2a biosynthesis might lead to increased fasting or postprandial glucose levels in patients with type 2 diabetes.…”

Pharmacodynamics Drug Interactions of Metformin with Aspirin and Nifedipine

“…It is claimed that Aspirin can cause decrease in basal rates of hepatic glucose production, enhances tissue insulin sensitivity, decreases insulin clearance, and decreases oxidative stress in diabetic patients 17,18 . In this study Nifedipine produced highly significant reduction (P> 0.001) in body weight in the rats with STZ induced hyperglycemia.…”