Investigating the effects of Orthosiphon stamineus on blood glucose regulation via pancreatic endocrine and exocrine functions in Type 3c Diabetes Mellitus Wistar Bonn/Kobori (WBN/Kob) pancreatitis rat model.

Background Type 3c diabetes mellitus (T3cDM) or pancreatogenic diabetes, results from pancreatic diseases such as chronic pancreatitis, pancreatic cancer or pancreatic surgery. Unlike type 1 and type 2 diabetes, T3cDM involves dysfunction of both pancreatic endocrine hormones (insulin, glucagon, pancreatic polypeptide, ghrelin, and somatostatin) and exocrine enzymes (amylase, lipase, and trypsinogen), causing impaired glucose regulation and nutrient malabsorption. Despite the widespread use of medicinal plants in diabetes management, evidence for their role in T3cDM, particularly in restoring exocrine pancreatic function, remains limited. This study aims to investigate the effects of Orthosiphon stamineus (OS) on glucose regulation through pancreatic endocrine and exocrine functions, as well as pancreatic islet integrity, using the Wistar Bonn/Kobori (WBN/Kob) rat model of T3cDM. Methods This double-blind, randomized, controlled preclinical study will follow ARRIVE 2.0 guidelines. Fifty rats will be allocated into five groups (n = 10/group): Control non-diabetic Wistar and T3cDM (Control, OS-treated, positive control and positive control with OS-treated) groups. Oral glucose tolerance test (OGTT) will be performed before and after one month of treatment. Blood glucose will be measured at 0, 30, 60, 90, and 120 minutes, while serum insulin will be assessed at 0, 30, and 120 minutes. Pancreatic endocrine hormones, exocrine enzymes, HbA1c and lipid-soluble vitamins will be quantified. Pancreatic islet integrity will be evaluated by immunohistology and immunohistochemistry. Primary outcomes include blood glucose, insulin and HbA1c, whereas secondary outcomes include endocrine hormones, exocrine enzymes, fat-soluble vitamins, body weight, clinical observations and histopathological changes. Expected Results We hypothesize that OS may improve glycemic regulation by enhancing pancreatic endocrine and exocrine functions, thereby promoting digestion, nutrient absorption and fat-soluble vitamin uptake. Conclusion This study protocol examines the efficacy of OS in addressing both exocrine and endocrine pancreatic dysfunction to improve blood glucose regulation, which ultimately improve the health strategies of T3cDM patients and enhance patient outcomes.