Interleukin-1 receptor antagonist improves normoglycemia and insulin sensitivity in diabetic Goto-Kakizaki-rats.
Type 2 diabetes mellitus has been considered as an auto-inflammatory syndrome. Interleukin-1 receptor antagonist (IL-1Ra) has attained considerable attention due to its broad spectrum anti-inflammatory therapeutic effects against various auto-immune diseases. The purpose of our study was to investigate its therapeutic effects of IL-1Ra on none-obese diabetic Goto-Kakizaki (GK) rats. We administered IL-1Ra subcutaneously for one month into GK rats. Insulin sensitivity and β-cell function was calculated by homeostatic model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) models. IL-1Ra decreased the onset of hyperglycemia and did not impact the body weight and/or food intake. Insulin tolerance test (ITT) and intraperitoneal glucose tolerance test (IPGTT) results showed that IL-1Ra improved insulin sensitivity and glucose tolerance. The results of HOMA and QUICKI models revealed that IL-1Ra improved insulin sensitivity and β-cell function. Moreover, significant reduction of pro-insulin/insulin ratio and lipid profiles also exhibited significant therapeutic effects of IL-1Ra. Immunohistochemical analysis showed minimal macrophage infiltration in pancreatic islets demonstrating decreased intra-islet inflammation in IL-1Ra treated GK rats. The results of our present study revealed that IL-1Ra has broad spectrum therapeutic potentials but due to its short biological half-life (6-8h) high doses with frequent dosing intervals are required. Therefore, there is a need for the development of such dosage form that may prolong its half-life via extended release.
College of Pharmaceutical Sciences, Zhejiang University Hangzhou, Hangzhou, China.
Muhammad Sajid Hamid
MS
Akash
Kanwal
K
Rehman
Hongyin
H
Sun
Shuqing
S
Chen
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors*; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D017472:Receptors, Interleukin-1; C067980:CD68 antigen, human; D000097382:CD68 Molecule