Inclusion of low amounts of fructose with an intraportal glucose load increases net hepatic glucose uptake in the presence of relative insulin deficiency in dog

Abstract

-The effect of small amounts of fructose on net hepatic glucose uptake (NHGU) during hyperglycemia was examined in the presence of insulinopenia in conscious 42-h fasted dogs. During the study, somatostatin (0.8 g ⅐ kg Ϫ1 ⅐ min Ϫ1 ) was given along with basal insulin (1.8 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) and glucagon (0.5 ng ⅐ kg Ϫ1 ⅐ min Ϫ1 ). After a control period, glucose (36.1 mol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) was continuously given intraportally for 4 h with (2.2 mol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) or without fructose. In the fructose group, the sinusoidal blood fructose level (nmol/ml) rose from Ͻ16 to 176 Ϯ 11. The infusion of glucose alone (the control group) elevated arterial blood glucose (mol/ml) from 4.3 Ϯ 0.3 to 11.2 Ϯ 0.6 during the first 2 h after which it remained at 11.6 Ϯ 0.8. In the presence of fructose, glucose infusion elevated arterial blood glucose (mol/ml) from 4.3 Ϯ 0.2 to 7.4 Ϯ 0.6 during the first 1 h after which it decreased to 6.1 Ϯ 0.4 by 180 min. With glucose infusion, net hepatic glucose balance (mol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) switched from output (8.9 Ϯ 1.7 and 13.3 Ϯ 2.8) to uptake (12.2 Ϯ 4.4 and 29.4 Ϯ 6.7) in the control and fructose groups, respectively. Average NHGU (mol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) and fractional glucose extraction (%) during last 3 h of the test period were higher in the fructose group (30.6 Ϯ 3.3 and 14.5 Ϯ 1.4) than in the control group (15.0 Ϯ 4.4 and 5.9 Ϯ 1.8). Glucose 6-phosphate and glycogen content (mol glucose/g) in the liver and glucose incorporation into hepatic glycogen (mol glucose/g) were higher in the fructose (218 Ϯ 2, 283 Ϯ 25, and 109 Ϯ 26, respectively) than in the control group (80 Ϯ 8, 220 Ϯ 31, and 41 Ϯ 5, respectively). In conclusion, small amounts of fructose can markedly reduce hyperglycemia during intraportal glucose infusion by increasing NHGU even when insulin secretion is compromised. diabetes mellitus; hyperglycemia; hyperinsulinemia INDIVIDUALS WITH TYPE 2 DIABETES MELLITUS exhibit excessive postprandial hyperglycemia with a defect in meal-or glucoseinduced suppression of endogenous glucose production (18,21,28,34). Several studies (21,28,34) have demonstrated that the greater net splanchnic glucose release in diabetic compared with nondiabetic subjects after glucose injection was due to excessive endogenous glucose production rather than lower initial splanchnic extraction of the ingested glucose. However, the insulin and glucose concentrations differed in the diabetic and nondiabetic subjects in all of those studies, precluding direct comparison of the efficiency of splanchnic glucose uptake. DeFronzo et al. (15) (15), found decreased splanchnic glucose uptake in diabetic subjects. It is known, however, that in the presence of euglycemia and hyperinsulinemia, there is minimal splanchnic glucose uptake (14,15,23,42). Thus the size of the signal in the above studies was very small. Hyperglycemia combined with hyperinsulinemia, on the other hand, substantially increases glucose uptake by the liver (14,23,42). Recently, Basu et al. (5) carried out a hyperglycemic and hyperins...

Honey and Diabetes: The Importance of Natural Simple Sugars in Diet for Preventing and Treating Different Type of Diabetes

“…Different studies were made on the effect of fructose on glycemic control, glucose-regulating hormones, appetite-regulating hormones, body weight, food intake, and oxidation of carbohydrates or energy expenditure [ 38 , 44 , 48 – 61 ].…”

Honey - A Novel Antidiabetic Agent

“…Increased hepatic glycogen synthesis via activation of glycogen synthase produced by fructose administration in diabetic and non-diabetic rats has been reported 101, 103. Evidence has also implicated the complementary and synergistic role of fructose and glucose on key enzymes involved in the metabolism of glucose and glycogen in the liver 104, 105. Evidence indicates that these monosaccharides produce a synergistic effect in the liver only when present or administered at a low or moderate dose or concentration 106.…”

A defect in glucose-induced dissociation of glucokinase from the regulatory protein in Zucker diabetic fatty rats in the early stage of diabetes

“…The binding of F-6-P to GKRP is required for the rat isoform of the protein to bind GK, and displacement of F-6-P by F-1-P at the common binding site on GKRP dissociates GK from GKRP by decreasing the affinity of the protein for GK (9,58). Small amounts of sorbitol or fructose, precursors of F-1-P, cause GK translocation from the nucleus to the cytoplasm and an increase in glucose phosphorylation and glycogen synthesis from glucose in cultured hepatocytes (2) during a euglycemic-hyperinsulinemic clamp in healthy humans (46) and in the presence of hyperglycemia with and without hyperinsulinemia in conscious normal dogs (49,50). To test our hypothesis that the failure of the elevated glucose to stimulate the dissociation of GK-GKRP complex and subsequent redistribution of GK to the cytoplasm in hepatocytes is responsible for both the impaired suppression of NHGP and a defect in HGU in response to a rise in plasma glucose in prediabetic ZDF rats, we examined the effect of small amounts of sorbitol on GK localization, impaired glucose-induced suppression of NHGP and stimulation of HGU in ZDF rats in the early stage of diabetes.…”