Metabolic Fate of the Glucose Taken up by the Intestine During Induced Hyperglycaemia in Dogs.

Available data showed that the intestine increases it glucose uptake in response to hyperglycemia induced by anycause. However, what the intestine does with the glucose is not known. This study investigated the metabolic fate of theglucose taken up by the intestine during hyperglycaemia in dogs. Experiments were carried out on fasted, male, anaesthetizedmongrel dogs divided into 4 groups. The control (group 1, n=5) received normal saline (0.2 ml/kg) while groups 2-4(subdivided into two as low or high dose, n=5 each) received adrenaline (1 µg/kg or 5 µg/kg), glucagon (3 ng/kg or 8 ng/kg)and glucose (10 mg/kg/min or 20 mg/kg/min). Through a midline laparatomy, the upper jejunum was cannulated for IntestinalBlood Flow (IBF) measurement. Blood glucose and lactate levels were determined using glucose oxidase and lactatedehydrogenase methods, respectively. Intestinal Glucose/Lactate Uptake (IGU/ILU) was calculated as the product of IBFand arterio-venous glucose /lactate difference [(A-V) glucose/lactate]. Jejunal tissue samples were obtained for the determinationof Glycogen Content (GC) and activities of Glycogen Synthase (GS), Glycogen Phosphorylase 'a' (GPa), hexokinase andglucose-6-phosphatase. Anthrone method was used to determine GC while activities of GS, GPa, hexokinase and glucose-6-phosphatase were determined spectrophotometrically. Data were subjected to descriptive statistics and analyzed usingstudent's t-test and ANOVA at α0.05. Arterial and venous blood glucose and lactate were increased by adrenaline, glucagonand glucose. Venous lactate was higher than arterial lactate in all groups. Intestinal blood flow, (A-V) glucose and (A-V)lactate were increased in all the experimental groups. Intestinal glucose uptake increased by 624% (adrenaline), 705%(glucagon) and 589% (glucose) while intestinal lactate release increased by 422%, 459% and 272% respectively. IntestinalGC increased from 138.72 ± 4.58 mg/100 g to 167.17 ± 4.20 mg/100 g (adrenaline), 229.21 ± 6.25 mg/100 g (glucagon) and165.17 ± 4.20 mg/100 g (glucose). Adrenaline and glucose had no effect on GS activity but it was increased by glucagon;GPa was decreased while hexokinase activity was increased by adrenaline, glucagon, and glucose. Glucose-6-phosphataseactivity was not affected by adrenaline and glucagon but decreased by glucose. The intestine modulates blood glucose levelsthrough lactate formation, glycogen formation and most probably conversion of lactate to glucose through gluconeogenesis.

Intestinal glucose uptake responses to infusion of glucose, fructose and galactose in dogs Intestinal glucose uptake responses to infusion of glucose, fructose and galactose in dogs.

The present study was designed to investigate the effects of intravanous (i.v) infusion of fructose, galactose and glucose on canine IGU during postprandial state. Experiments were carried out on fasted, male, anaesthethized adult mongrel dogs divided into four groups with 5 dogs per group. Each of the groups was given i.v infusion of normal saline, fructose (0.15, 0.55 and 1.1mg/dl/min), galactose (0.15, 0.55 and 1.1mg/dl/min) and glucose (0.15, 0.55 and 1.1mg/dl/min) respectively. Through a midline laparatomy, the upper jejunum was secured and cannulated for blood flow measurement. Blood samples were obtained for measurement of glucose content of arterial and venous blood from the upper jejunal segment. The blood glucose was determined by glucose oxidase method and intestinal glucose uptake was calculated as the product of jejunal blood flow and arterio-venous glucose difference. Values are means ± S.E.M, compared by ANOVA and Student t-test. Fructose, galactose and glucose significantly increased arterial blood glucose from 97.60 ± 1.78 mg/dl to 114.20 ± 1.88, 109.80 ± 1.43, and 141.20 ± 5.65 mg/dl, respectively. Glucose also significantly increased jejunal blood flow from 10.0 ± 0.32 ml/min to 14.40 ± 0.93 ml/min, however, fructose and galactose did not produce any significant effect on intestinal blood flow. IGU increased by 600%, 350%, and 700% in response to fructose, galactose and glucose respectively. There is no correlation between the increase in blood glucose levels induced by each of the sugars and its corresponding rise in IGU. The data suggest that the intestine responds to fructose and galactose in a similar manner as glucose probably through similar mechanism.

Role of Adrenergic Receptors in Glucose, Fructose and Galactose-Induced Increases in Intestinal Glucose Uptake in Dogs.

The study investigated the role of adrenergic receptors in glucose, fructose-, and galactose- induced increases in intestinal glucose uptake. Experiments were carried out on fasted male anaesthetized Nigerian local dogs divided into seven groups (with five dogs per group). Group I dogs were administered normal saline and served as control. Dogs in groups II, III and IV were intravenously infused with glucose (1.1 mg/kg/min), fructose (1.1 mg/kg/min) and galactose (1.1 mg/kg/min) respectively. Another three groups, V, VI and VII were pretreated with prazosin (0.2mg/kg), propranolol (0.5mg/kg) or a combination of prazosin (0.2mg/kg) and propranolol (0.5mg/kg) followed by glucose infusion, frutose infusion or galactose infusion respectively. Through a midline laparatomy, the upper jejunum was cannulated for blood flow measurement and blood samples were obtained for measurement of glucose content of the arterial blood and venous blood from the upper jejunal segment. Glucose uptake was calculated as the product of jejunal blood flow and the difference between arterial and venous glucose levels (A-V glucose). The results showed that pretreatment of the animal with prazosin had no effect on glucose and galactose induced increases in glucose uptake. However, pretreatment with propranolol completely abolished glucose, fructose and galactose-induced increases in intestinal glucose uptake. Prazosin also significantly reduced galactose-induced increase in intestinal glucose uptake. The results suggest that the increases in intestinal glucose uptake induced by glucose and fructose are mediated mostly by beta adrenergic receptors while that of galactose is mediated by both alpha and beta adrenergic receptors.

Effect of adrenaline on glucose uptake in the rabbit small intestine.

OBJECTIVES: Previous study had shown that nicotine acts on blood glucose through release of adrenaline. While there are reports on the hyperglyceic effect of adrenaline in rabbits, there is no information on the effect of adrenaline on intestinal glucose uptake of rabbits. The present study was carried out to find out if adrenaline has any effect on glucose uptake in the rabbit small intestine. MATERIALS AND METHODS: Experiments were carried out on fasted anaesthetized male rabbits. Five groups of rabbits (6 rabbits per group) were studied. A vein draining a segment of the upper jejunum was cannulated for blood flow and venous glucose measurements. The left femoral artery and vein were cannulated for arterial blood sampling and drug infusion respectively. Glucose uptake was calculated as a product of jejunal blood flow and the glucose difference between arterial (A) and venous (V) blood. RESULTS: The fasting venous blood glucose levels were 151.8 +/- 4.4mg/dl and 164.0 + 2.3mg/dl in Groups I and V that were not given adrenoceptor blockers. The upper jejunum had a resting (or basal) glucose uptake of 38.3 +/- 1.6mg/min in the control group. When adrenaline (2ug/kg) was injected intravenously, arterial blood glucose rose from a basal value of 245.5 +/- 4.6mg/dl to 307.5+4.7mg/dl at the peak of response while venous glucose rose from 151.8+4.4mg/dl to 275.8 +/- 4.2mg/dl at the peak of response. Glucose uptake increased to 107.4 +/- 2.5mg/ min at the peak of response. The hyperglycaemic response to adrenaline injection was abolished by propranolol but not by prazosin indicating that this effect of adrenaline is mediated through beta adrenoceptor. Both prazosin and propranolol reduced considerably adrenaline-induced increase in blood flow and glucose uptake, prazosin being more potent in flow reduction. CONCLUSION: This study showed that the resting small intestine of rabbits took up large amounts of glucose. The intestinal glucose uptake was markedly increased by adrenaline injection. The response to adrenaline was mediated through alpha and beta adrenoceptors. The responses to adrenaline are different in many respects from those induced by nicotine in rabbits in our earlier study. The reason for the differences is obscure.

Effect of nicotine on glucose uptake in the rabbit small intestine.

A technique for measuring glucose uptake in the small intestine of rabbits was developed. Using this technique, the glucose uptake in the resting jejunum of rabbits and the effect of nicotine infusion on glucose uptake were studied. Experiments were carried out on fasted anaesthetized male rabbits. Four groups of rabbits (6 per group) were studied. A vein draining segment of the upper jejunum was cannulated for blood flow and venous glucose measurements. The left femoral artery and vein were cannulated for arterial blood sampling and drug infusion respectively. Glucose uptake was calculated as a product of jejunal blood flow and the (A-V) glucose difference. The fasting blood glucose levels were 101.0 +/- 8.4 mg/dl and 127.0 +/- 11.3 mg/dl before and after anaesthesia respectively. Basal blood glucose was much higher than this following surgery. The upper jejunum had a resting glucose uptake of 24.1 +/- 7.0 mg/min. When nicotine (50 ug/kg) was infused intravenously, blood glucose rose from a basal value of 253.8 +/- 9.5 mg/dl to 379.8 +/- 20.3 mg/dl at the peak of response. Glucose uptake increased to 73.1 +/- 11.3 mg/min at the peak of response. These effects of nicotine are mediated through both beta and alpha adrenoceptors. Comparison with previous studies in dogs and rats showed that different adrenoceptors are involved in nicotine hyperglycaemia in fasted dogs, rats and rabbits.

Intestinal glucose uptake in normal, untreated and insulin-treated diabetic dogs.

The study was carried out on fasted, anaesthetized diabetic and non-diabetic dogs. Diabetes was induced by i.v injection of alloxan (60 mg/kg). A vein draining a segment of the upper jejunum was cannulated for blood flow measurements, and blood samples were obtained for determination of glucose content of arterial and venous blood. Glucose uptake was calculated as the product of jejunal blood flow and arterio-venous glucose difference ((A-V) glucose. The results showed that following induction of diabetes, there were significant increases in jejunal blood flow, (A-V) glucose and jejunal glucose uptake when compared with non-diabetic dogs. For instance, the glucose uptake increased from 23.10+/-2.34 to 178.40+/-6.93 mg/min. When the diabetic dog was challenged with different doses of insulin (2.5, 5.0, 7.5, 10.0 iu/kg), the blood glucose levels and the intestinal glucose uptake decreased in a dose-dependent manner. In normal dogs, insulin administration caused negative glucose uptake at the lower dose (5.0 iu/ kg) while at the higher dose, 8.0 iu/kg, insulin caused just a transient negative glucose uptake. From the results, it was concluded that the small intestine increased its glucose uptake in response to the hyperglycemia in alloxan-induced diabetes and when the blood glucose was reduced with insulin the intestine also reduced its glucose uptake accordingly. The result of insulin administration in normal dogs suggests that glucose uptake by the gut cannot be explained on the basis of blood glucose concentration alone.