Disordered expression of hepatic glycolytic and gluconeogenic enzymes in Itsuka long-evans Tokushima fatty rats with spontaneous long-term hyperglycemia

Hotta, Kikuko; Kuwajima, Masamichi; Ono, Akira; Nakajima, Hitoshi; Shingu, Ryosuke; Miyagawa, Jun‐ichiro; Namba, Mitsuyoshi; Hanafusa, Toshiaki; Noguchi, T.; Kôno, Norio; Matsuzawa, Yūji

doi:10.1016/0304-4165(95)00148-4

Cited by 15 publications

(9 citation statements)

References 29 publications

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“…It is unlikely, however, that the hepatic glucose output in OLETF rats was increased compared with that in LETO rats since the fasting IRI level as well as the insulin-induced in vivo glucose utilization was the same in the two strains in this study. The glucagon concentrations are also reported to be similar in young LETO and OLETF rats [19,27]. Thus, we hypothesize that the increment in intestinal glucose absorption may contribute to the postprandial hyperglycaemia in OLETF rats.…”

Section: Discussionsupporting

confidence: 59%

Increased intestinal glucose absorption and postprandial hyperglycaemia at the early step of glucose intolerance in Otsuka Long-Evans Tokushima Fatty Rats

et al. 1998

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Glucose intolerance is believed to be caused not only by insulin resistance but also impaired insulin secretion [1±3]. Dietary restrictions and exercise are effective in intervening in glucose intolerance, postprandial hyperglycaemia, and impaired insulin secretion [4,5]. a-glucosidase inhibitors, which delay intestinal glucose absorption, also improve postprandial hyperglycaemia and hyperinsulinaemia in Type II (non-insulin-dependent) diabetic patients [6] and prevent the progression from impaired glucose tolerance to Type II diabetes [7]. We therefore hypothesize that increased intestinal glucose absorption may be another possible factor regulating postprandial hyperglycaemia in diabetes mellitus. Diabetologia (1998) Summary Otsuka Long-Evans Tokushima Fatty (OLETF) rats are reported to be obese Type II (non-insulin-dependent) diabetic rats with insulin resistance and impaired insulin secretion. To investigate the contribution of intestinal glucose absorption to postprandial hyperglycaemia, we determined the plasma xylose concentrations after an 0.8 g/kg oral xylose load which was used as a test of small intestinal glucose absorption in 6-week-old OLETF rats and weight-matched Long-Evans Tokushima Otsuka (LETO) rats. An oral glucose tolerance test showed that OLETF rats developed hyperglycaemia at 60 and 90 min after the glucose load, though the fasting plasma glucose concentration, insulin concentration and insulin-induced in vivo glucose utilization rate were similar. Consistently, in an oral D-xylose loading test, the peak concentration of plasma xylose in OLETF rats was increased by 58.7 % compared with that of LETO rats (p < 0.005). The disappearance rate of plasma xylose concentrations after intravenous xylose loading did not differ between the two strains. Co-treatment with 0.4 g/kg phlorizin, a specific inhibitor of sodium-dependent glucose transporter 1 (SGLT1), abolished both plasma glucose and xylose concentrations after the loads. Morphological studies showed that both the small intestinal wet weight and surface area were 30 % larger in the OLETF rats than in the LETO rats. Furthermore, the SGLT1 mRNA content of OLETF rats also increased compared with LETO rats. These results suggest that an increased SGLT1 expression concomitant with intestinal hypertrophy in OLETF rats is partly associated with postprandial hyperglycaemia before the onset of insulin resistance and hyperinsulinaemia. [Diabetologia (1998

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Section: Discussionsupporting

confidence: 59%

Increased intestinal glucose absorption and postprandial hyperglycaemia at the early step of glucose intolerance in Otsuka Long-Evans Tokushima Fatty Rats

et al. 1998

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“…Despite hyperinsulinemia, hepatic G6Pase and FBPase activities in d b/d b mice, which were normally suppressed by the action of insulin (21), were increased compared with d b/+m mice. The increased activities of G6Pase and FBPase are considered to be important for the development of hyperglycemia in d b/d b mice, as suggested in previous reports (22)(23)(24)(25).…”

Section: Tablementioning

confidence: 74%

Dehydroepiandrosterone suppresses the elevated hepatic glucose-6-phosphatase and fructose-1,6-bisphosphatase activities in C57BL/Ksj-db/db mice: comparison with troglitazone.

et al. 1999

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The effect of dehydroepiandrosterone (DHEA) on the hepatic and muscle glucose metabolizing enzymes and on blood glucose were investigated in insulin-resistant diabetic C57BL/KsJ-db/db mice and their heterozygote littermates (db/+m). The results were compared with those after troglitazone administration under the same conditions. Despite hyperinsulinemia, hepatic glucose-6-phosphatase (G6Pase) and fructose-1,6-bisphosphatase (FBPase) activities are higher in db/db than in db/+m mice. Dietary administration of DHEA and that of troglitazone for 15 days to respective groups of five mice each significantly decreased blood glucose in db/db mice and hepatic G6Pase and FBPase activities in both db/db and db/+m mice. Hepatic G6Pase and FBPase activities showed a linear relationship with blood glucose in all groups of mice, suggesting that the activities of G6Pase and FBPase are closely related to blood glucose levels. Because androstenedione, a DHEA metabolite, barely affected either of these enzyme activities or blood glucose in db/db mice, the actions of DHEA, which are similar to those of troglitazone, are presumed to be caused by DHEA itself. DHEA is considered to be a modulating agent for the activities of hepatic gluconeogenic enzymes in db/db mice.

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“…Evidence is available that chronic hyperglycemia upregulates the expression of glucose-6-phosphatase (45) and that suppression of EGO by glucose itself is impaired in type 2 diabetes (39). On the other hand, the ability of insulin to control the activity of glucose-6-phosphatase and to depress the expression of PEP-carboxykinase (46) is com-promised in diabetes (47,48). Thus, the increase in GNG activity in diabetes is likely to be multifactorial in origin, with both primary defects and adaptive changes.…”

Section: Discussionmentioning

confidence: 99%

Influence of obesity and type 2 diabetes on gluconeogenesis and glucose output in humans: a quantitative study.

et al. 2000

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The contribution of gluconeogenesis (GNG) to endogenous glucose output (EGO) in type 2 diabetes is controversial. Little information is available on the separate influence of obesity on GNG. We measured percent GNG (by the 2 H 2 O technique) and EGO (by 6,6-[ 2 H]glucose) in 37 type 2 diabetic subjects (9 lean and 28 obese, mean fasting plasma glucose [FPG] 8.3 ± 0.3 mmol/l) and 18 control subjects (6 lean and 12 obese) after a 15-h fast. Percent GNG averaged 47 ± 5% in lean control subjects and was significantly increased in association with both obesity (P < 0.01) and diabetes (P = 0.004). By multivariate analysis, percent GNG was independently associated with BMI (partial r = 0.27, P < 0.05, with a predicted increase of 0.9% per BMI unit) and FPG (partial r = 0.44, P = 0.0009, with a predicted increase of 2.7% per mmol/l of FPG). In contrast, EGO was increased in both lean and obese diabetic subjects (15.6 ± 0.5 µmol · min -1 · kg -1 of fat-free mass, n = 37, P = 0.002) but not in obese nondiabetic control subjects (13.1 ± 0.7, NS) as compared with lean control subjects (12.4 ± 1.4). Consequently, gluconeogenic flux (percent GNG ؋ EGO) was increased in obesity (P = 0.01) and markedly elevated in diabetic subjects (P = 0.0004), whereas glycogenolytic flux was reduced only in association with obesity (P = 0.05). Fasting plasma glucagon levels were significantly increased in diabetic subjects (P < 0.05) and positively related to EGO, whereas plasma insulin was higher in obese control subjects than lean control subjects (P = 0.05) and unrelated to measured glucose fluxes. We conclude that the percent contribution of GNG to glucose release after a 15-h fast is independently and quantitatively related to the degree of overweight and the severity of fasting hyperglycemia. In obese individuals, reduced glycogenolysis ensures a normal rate of glucose output. In diabetic individuals, hyperglucagonemia contributes to inappropriately elevated rates of glucose output from both GNG and glycogenolysis. Diabetes 49:1367-1373, 2000 P atients with type 2 diabetes typically show an increase in endogenous glucose output (EGO) (1-3). Several observations indicate that gluconeogenesis (GNG) is increased in type 2 diabetes. First, there is an increased protein turnover and hence release of gluconeogenic amino acids. Second, in obese patients with type 2 diabetes, the increased fat mass and rate of lipolysis contribute substrate (glycerol) (4,5) and activation (free fatty acids) (6,7) for GNG. Third, the net uptake of all gluconeogenic precursor substrates by the liver is increased. Using splanchnic catheterization, Felig et al. (8) estimated that in diabetic subjects, conversion into glucose of gluconeogenic precursors could represent 30% of splanchnic glucose output versus 20% in lean nondiabetic subjects (8). Although net splanchnic substrate uptake cannot account for the whole of GNG, this finding is nevertheless compatible with enhanced GNG in diabetes. Finally, tracer studies have shown that in obese type 2 diabetic patients...

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Disordered expression of hepatic glycolytic and gluconeogenic enzymes in Itsuka long-evans Tokushima fatty rats with spontaneous long-term hyperglycemia

Cited by 15 publications

References 29 publications

Increased intestinal glucose absorption and postprandial hyperglycaemia at the early step of glucose intolerance in Otsuka Long-Evans Tokushima Fatty Rats

Increased intestinal glucose absorption and postprandial hyperglycaemia at the early step of glucose intolerance in Otsuka Long-Evans Tokushima Fatty Rats

Dehydroepiandrosterone suppresses the elevated hepatic glucose-6-phosphatase and fructose-1,6-bisphosphatase activities in C57BL/Ksj-db/db mice: comparison with troglitazone.

Influence of obesity and type 2 diabetes on gluconeogenesis and glucose output in humans: a quantitative study.

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