THE ROLE OF THE GASTROINTESTINAL TRACT IN GLUCOSE HOMEOSTASIS

Abstract

This study was designed to investigate the role of the gastrointestinal tract in glucose handling during hyperglycaemia induced by infusion of glucose, injection of glucagon or adrenaline and during insulin -induced hypoglycaemia. The study was carried out on fasted anaethetized dogs. Anaesthesia was induced by Intravenous sodium pentobarbitone, 30mg/kg. The trachea of the animal was intubated with a Y- piece cannula to allow the animal to breathe room air. A cannula was placed in the carotid artery to monitor blood pressure using a pressure transducer connected to a dymograph (R511A). Cannulae were also placed in the right femoral vein and right femoral artery. Through a midline laparotomy, a vein draining the proximal segment of the jejunum was cannulated using a 1.8mm (i.d) polyethylene. tubing (P.E. 260). Anti coagulation was maintained with i.v. injection of heparin, 300 units per kg. The abdomen was closed in two layers with Interrupted sutures. A period of 60-90 min was then allowed for the animal to stabilize. After stabilization, basal measurements of Jejunal venous blood flow, arterial and venous glucose levels were made at five minute intervals over 15 minutes. Jejunal blood flow was determined by timed collection. Arterial and venous blood samples for glucose estimation were obtained from the femoral artery and jejunal venous cannulae respectively. Blood glucose was determined by the modified glucose oxidase method (Trinder, 1969). Glucose uptake was calculated as the product of blood flow and arterio venous (A -V) glucose difference. Blood pressure was recorded continuously throughout the duration of the experiment. Jejunal vascular resistance was calculated by dividing the blood pressure by the blood flow rate. The experiments were first performed on five groups of untreated dogs (with five dogs per group). Group I dogs were given i.v. injection of adrenaline, 1ug or 5ug per kg. Group II dogs had i.v. injection of glucagon 3ng or 8ng per kg. Group III animals were also given i.v. infusion of glucose, 10mg or 20mg per kg per min. Group IV animals had i.v. injection of insulin, 5i.u or 8i.u per kg and Group V animals were given i.v. injection of normal saline (0.2ml/kg) and served as the control. In each group, blood pressure and blood flow rate measurements were recorded, while the arterial and venous blood samples for glucose estimation were obtained at timed interval for 1 hour post injection. The role of adrenergic receptors in the responses observed was then investigated by pretreating the animal with prazosin (0.2mg per kg), propranolol (0.5mg per kg) or a combination of the two blockers followed by injection or infusion of adrenaline, glucagon, glucose or insulin as in Groups I to IV. The procedure for blood pressure recording, blood flow measurement and blood samples collection from femoral artery and jejunal vein were also repeated as in the untreated groups. The results showed that adrenaline caused increased intestinal glucose uptake of 600% and 700% for the low and high doses respectively. Glucagon also caused increased intestinal glucose uptake of 700% and 900% after injection of low dose and high dose of glucagon respectively, while glucose infusion resulted in an increase of 560% and 600% for low and high doses of glucose respectively. Insulin, however, caused a negative uptake of about -280% and -400% for the low and high doses respectively. Propranolol caused a significant reduction in the increase in intestinal glucose uptake caused by adrenaline, glucagon, glucose or insulin. Prazosin however, had no effect on the glucose uptake except In adrenaline experiments where it caused a significant reduction in adrenaline-induced increase in intestinal glucose uptake. Arterial blood pressure rose from a basal value of 120.31 ±1.20 to peak values of 173.30± 4.75, 132.00 ± 3.19 and 136.10 ± 3.99mmHg following injection of adrenaline, glucagon and insulin respectively. Glucose infusion caused no significant change in blood pressure. Blood flow measurement showed that adrenaline, glucagon, glucose and Insulin increased jejunal blood flow rate from basal level of 9.50 ± 0.29 to 15.90 ± 2.06, 12.10 ± 0.89, 10.86 ± 0.96 and 10.10 ± 0.19ml/min respectively. The vascular resistance fell during this period. The results were discussed and the conclusion from the study supports the hypothesis that the gestrointestinal tract plays a major role in glucose homeostasis and that the process is mediated mainly through beta adrenoceptors.