Disrupted cholecystokinin type-A receptor (CCKAR) gene in OLETF rats

Takiguchi, Soichi; Takata, Yutaka; Funakoshi, Akihiro; Miyasaka, Kyoko; Kataoka, Koichi; Fujimura, Yoshiteru; Goto, Toshihiro; Kono, Akira

doi:10.1016/s0378-1119(97)00259-x

Cited by 164 publications

(113 citation statements)

References 31 publications

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“…OLETF female rats lost fat during the lactation period, from all the three examined tissues. In the middle of the lactation period and during the transition toward weaning (days [15][16][17][18][19][20][21][22], OLETF dams had reduced weight fat tissues that did not differ from those of LETO controls in the same lactation stage. In contrast, 8 weeks PW OLETF dams gained fats, appearing to re-achieve the same amount as observed in NP.…”

Section: Adipose Tissuesmentioning

confidence: 90%

“…To elucidate the contribution of CCK, leptin and OT to adaptation to lactation, we used genetically obese Otsuka Long Evans Tokushima Fatty (OLETF) rats, lacking expression of functional CCK-1 receptors. 18,19 In the absence of functional peripheral short-term CCK satiety signaling, male OLETF rats eat large meals, accumulate larger fat pads and become obese. Meal size of OLETF male rats is double than that of Long Evans Tokushima Otsuka (LETO) controls, although meal number decreases, but not to a sufficient degree to prevent overweight.…”

Section: Introductionmentioning

confidence: 99%

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Adaptation to lactation in OLETF rats lacking CCK-1 receptors: body weight, fat tissues, leptin and oxytocin

et al. 2008

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Objective: To understand the adaptation to lactation of obese rats, by studying the interplay among the gut hormone cholecystokinin (CCK), the adiposity hormone leptin and the affiliation hormone oxytocin in modulating body mass and fat storage. Design: Strain differences were examined between Otsuka Long Evans Tokushima Fatty (OLETF) rats lacking expression of functional CCK-1 receptors and Long Evans Tokushima Otsuka (LETO) controls, tested as nulliparous dams, at the 7 and 15th lactation day, at weaning (lactation day 22) or 8 weeks postweaning. Measurements: We measured body mass, fat pads (brown, retroperitoneal and inguinal) and inguinal adipocytes. Plasma levels of leptin and oxytocin were determined. Results: Fat depots of LETO female rats were larger during lactation compared to the levels found in postweaning and nulliparous female rats. LETO female rats gained weight and accumulated fat during pregnancy and lactation, returning to their normal fat levels postweaning. In contrast, OLETF female rats presented lower body weight and fat depots during the lactation period than nulliparous dams, and regained the weight and fat postweaning. Plasma leptin and oxytocin were highly correlated and followed the same pattern. OLETF leptin levels were highly correlated with fat depot and inguinal cell surface. No significant correlation was found for LETO parameters. Conclusions: Pregnancy and lactation are energy-consuming events, which naturally induce female rats to increase food intake and accumulate fat. When challenged by the demands of rapidly growing preobese OLETF pups, OLETF dams' fat stores are reduced to lean, LETO levels. During lactation, sensitivity of the oxytocinergic neurons descending from the paraventricular nuclei to the nucleus of the solitary tract to CCK is reduced. We theorized that this pathway is not available to OLETF female rats that lack functional CCK-1 receptors to mediate the signal. The current study contributes to the understanding of the female body's adaptation to lactation.

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Section: Adipose Tissuesmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Adaptation to lactation in OLETF rats lacking CCK-1 receptors: body weight, fat tissues, leptin and oxytocin

et al. 2008

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“…Our results indicated that the intestinal hypertrophy was observed in 6-weekold OLETF rats which showed postprandial hyperglycaemia with normal fasting plasma glucose and insulin concentrations. It has been noted in OLETF rats that a CCK-A receptor is genetically affected because of the gene deletion [36] and that the proliferation of pancreatic beta cells is also impaired in regenerative growth [37]. Other diabetogenic genes were screened in those rats and it has recently been reported that the CCK-A receptor gene is found to be similar to one of these genes, OBD-2 gene, by a linkage analysis using microsatellite markers [38].…”

Section: Discussionmentioning

confidence: 99%

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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“…24 This strain manifests obesity, elevated BP, insulin resistance and dyslipidemia, and thus well serves as a model of metabolic syndrome. 10,11 We and others showed the consequences of such metabolic abnormalities, including impaired coronary-vasodilatory function 19 and left ventricular-diastolic dysfunction, 17 which were attributable to impaired nitric oxide/superoxide balance and enhanced expression of redox-sensitive prolifero-inflammatory cytokines.…”

Section: Oletf Rats As a Model Of Metabolic Syndromementioning

confidence: 99%

Effects of combined olmesartan and pravastatin on glucose intolerance and cardiovascular remodeling in a metabolic-syndrome model

et al. 2009

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Hypertension and dyslipidemia frequently coexist in patients with progressive insulin resistance and thus constitute metabolic syndrome. We sought to determine the merits of combining an angiotensin II receptor blocker and a 3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitor in treating this pathological condition. Five-week-old Otsuka Long-Evans Tokushima Fatty rats, a model of metabolic syndrome, were untreated or treated with olmesartan 3 mg kg À1 per day, pravastatin 30 mg kg À1 per day or their combination for 25 weeks. Long-Evans Tokushima Otsuka rats served as normal controls. The antihypertensive effect of olmesartan and the lipid-lowering properties of pravastatin were both augmented by the combination. The oral glucose tolerance test revealed that only the combined treatment significantly reduced the area under the time-glucose curve, which was accompanied by augmented adiponectin messenger RNA expression in epididymal adipose tissue. Although the total cardiac endothelial nitric oxide synthetase (eNOS) content did not significantly differ among the groups, the combined treatment significantly increased the content of dihydrofolate reductase, a key eNOS coupler. Dihydroethidium staining of the aorta showed that the combination most significantly attenuated superoxide production. Moreover, Azan-Mallory staining revealed that the combination most significantly limited the perivascular fibrosis and wall thickening of intramyocardial coronary arteries. In conclusion, the combination of olmesartan and pravastatin augmented adiponectin expression in white adipose tissue and improved glucose tolerance in a rat model of metabolic syndrome, which was associated with more significant ameliorations of cardiovascular redox state and remodeling than those by treatments with either agent alone.

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Disrupted cholecystokinin type-A receptor (CCKAR) gene in OLETF rats

Cited by 164 publications

References 31 publications

Adaptation to lactation in OLETF rats lacking CCK-1 receptors: body weight, fat tissues, leptin and oxytocin

Adaptation to lactation in OLETF rats lacking CCK-1 receptors: body weight, fat tissues, leptin and oxytocin

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

Effects of combined olmesartan and pravastatin on glucose intolerance and cardiovascular remodeling in a metabolic-syndrome model

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