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

Fujita, Yukihiro; Kojima, Hideto; Hidaka, Hideki; Fujimiya, Mineko; Kashiwagi, Atsunori; Kikkawa, Ryuichi

doi:10.1007/s001250051092

Cited by 78 publications

(60 citation statements)

References 40 publications

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“…Although the dual tracer approach used in the present experiments cannot distinguish between these two processes, the portal rate of appearance of enterically delivered glucose was slightly (but not significantly) lower in the diabetic subjects than in the nondiabetic subjects. This contrasts with reports that glucose absorption (25) and intestinal transport (49,50) are enhanced in chronically diabetic animals. Although this could be due to a species difference, it more likely is because the diabetic animals generally were severely hyperglycemic and hyperphagic, which presumably led to intestinal hypertrophy (51).…”

Section: Discussioncontrasting

confidence: 99%

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Type 2 Diabetes Impairs Splanchnic Uptake of Glucose but Does Not Alter Intestinal Glucose Absorption During Enteral Glucose Feeding

et al. 2001

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We have previously reported that splanchnic glucose uptake, hepatic glycogen synthesis, and hepatic glucokinase activity are decreased in people with type 2 diabetes during intravenous glucose infusion. To determine whether these defects are also present during more physiological enteral glucose administration, we studied 11 diabetic and 14 nondiabetic volunteers using a combined organ catheterization-tracer infusion technique. Glucose was infused into the duodenum at a rate of 22 mol ⅐ kg ؊1 ⅐ min ؊1 while supplemental glucose was given intravenously to clamp glucose at ϳ10 mmol/l in both groups. Endogenous hormone secretion was inhibited with somatostatin, and insulin was infused to maintain plasma concentrations at ϳ300 pmol/l (i.e., twofold higher than our previous experiments). Total body glucose disappearance, splanchnic, and leg glucose extractions were markedly lower (P < 0.01) in the diabetic subjects than in the nondiabetic subjects. UDP-glucose flux, a measure of glycogen synthesis, was ϳ35% lower (P < 0.02) in the diabetic subjects than in the nondiabetic subjects. This was entirely accounted for by a decrease (P < 0.01) in the contribution of extracellular glucose because the contribution of the indirect pathway to hepatic glycogen synthesis was similar between groups. Neither endogenous and splanchnic glucose productions nor rates of appearance of the intraduodenally infused glucose in the portal vein differed between groups. In summary, both muscle and splanchnic glucose uptake are impaired in type 2 diabetes during enteral glucose administration. The defect in splanchnic glucose uptake appears to be due to decreased uptake of extracellular glucose, implying decreased glucokinase activity. Thus, abnormal hepatic and muscle (but not gut) glucose metabolism are likely to contribute to postprandial hyperglycemia in people with type 2 diabetes. Diabetes 50:1351-1362, 2001

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Section: Discussioncontrasting

confidence: 99%

“…Experimental diabetes in animals has been reported to enhance glucose absorption (25) and increase intestinal glucose metabolism. It is currently not known whether the same phenomenon occurs in diabetic humans.…”

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confidence: 99%

Type 2 Diabetes Impairs Splanchnic Uptake of Glucose but Does Not Alter Intestinal Glucose Absorption During Enteral Glucose Feeding

et al. 2001

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“…At the end of a 120-min period, we collected blood (100, 110, and 120 min) to measure the hepatic glucose production and peripheral glucose disposal rates (20,21). A high dose hyperinsulinemic-euglycemic clamp was then started using 10 milliunits/kg/min insulin infusion and continued for 120 min to measure in vivo glucose utilization according to the method of Fujita et al (22) with slight modification. We monitored the plasma glucose level every 3 min.…”

Section: Methodsmentioning

confidence: 99%

Metabolic Adaptations in the Absence of Perilipin

Saha

Kojima

Martı́nez-Botas

et al. 2004

Journal of Biological Chemistry

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Targeted disruption of the lipid droplet protein, perilipin, in mice leads to constitutional lipolysis associated with marked reduction in white adipose tissue as a result of unbridled lipolysis. To investigate the metabolic adaptations in response to the constitutive lipolysis, we studied perilipin-null (plin ؊/؊ ) mice in terms of their fatty acid oxidation and glycerol and glucose metabolism homeostasis by using dynamic biochemical testing and clamp and tracer infusion methods. plin ؊/؊ mice showed increased ␤-oxidation in muscle, liver, and adipose tissue resulting from a coordinated regulation of the enzymes and proteins involved in ␤-oxidation. The increased ␤-oxidation helped remove the extra free fatty acids created by the constitutive lipolysis. An increase in the expression of the transcripts for uncoupling proteins-2 and -3 also accompanied this increase in fatty acid oxidation. Adult plin ؊/؊ mice had normal plasma glucose but a reduced basal hepatic glucose production (46% that of plin ؉/؉ ). Insulin infusion during low dose hyperinsulinemic-euglycemic clamp further lowered the glucose production in plin ؊/؊ mice, but plin ؊/؊ mice also showed a 36% decrease (p < 0.007) in glucose disposal rate during the low dose insulin clamp, indicating peripheral insulin resistance. However, compared with plin ؉/؉ mice, 14-week-old plin ؊/؊ mice showed no significant difference in glucose disposal rate during the high dose hyperinsulinemic clamp, whereas 42-week-old plin ؊/؊ mice displayed significant insulin resistance on high dose hyperinsulinemic clamp. Despite increasing insulin resistance with age, plin ؊/؊ mice at different ages maintained a normal glucose response during an intraperitoneal glucose tolerance curve, being compensated by the increased ␤-oxidation and reduced hepatic glucose production. These experiments uncover the metabolic adaptations associated with the constitutional lipolysis in plin ؊/؊ mice that allowed the mice to continue to exhibit normal glucose tolerance in the presence of peripheral insulin resistance.Obesity is a growing health problem with significant associated morbidity and mortality. Although obesity can result from environmental factors and a sedentary life-style, recent findings suggest that susceptibility to obesity is to a large extent genetically determined (1). One approach to study obesity and its associated morbidity is to investigate genes and pathways involved in the regulation of lipid metabolism and body fat deposition. A fat cell protein, perilipin, has recently been found to play a key role in determining body habitus as its absence leads to a lean and obesity-resistant phenotype in mice (2, 3). Perilipin belongs to a class of proteins found exclusively at the limiting surface of storage droplets in adipocytes and in steroidogenic cells (4 -7). It coats the lipid droplets and protects triglycerides from the lipolytic action of hormone-sensitive lipase (6). Hormone-sensitive lipase catalyzes the breakdown of triacylglycerols and the release of free fatty acids ...

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“…5c). Since xylose is absorbed through SGLT1 in the intestine and is not metabolized, the xylose absorption test reflects the activity of SGLT1 (Fujita et al 1998). We then measured plasma xylose concentrations.…”

Section: Gip Secretion By Carbohydrates Is Enhanced Inmentioning

confidence: 99%

KATP channel as well as SGLT1 participates in GIP secretion in the diabetic state

Ogata¹,

Seino²,

Harada³

et al. 2014

Journal of Endocrinology

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Glucose-dependent insulinotropic polypeptide (GIP), a gut hormone secreted from intestinal K-cells, potentiates insulin secretion. Both K-cells and pancreatic b-cells are glucoseresponsive and equipped with a similar glucose-sensing apparatus that includes glucokinase and an ATP-sensitive K C (K ATP ) channel comprising KIR6.2 and sulfonylurea receptor 1. In absorptive epithelial cells and enteroendocrine cells, sodium glucose co-transporter 1 (SGLT1) is also known to play an important role in glucose absorption and glucose-induced incretin secretion. However, the glucose-sensing mechanism in K-cells is not fully understood. In this study, we examined the involvement of SGLT1 (SLC5A1) and the K ATP channels in glucose sensing in GIP secretion in both normal and streptozotocin-induced diabetic mice. Glimepiride, a sulfonylurea, did not induce GIP secretion and pretreatment with diazoxide, a K ATP channel activator, did not affect glucose-induced GIP secretion in the normal state. In mice lacking K ATP channels (Kir6.2 K/K mice), glucose-induced GIP secretion was enhanced compared with control (Kir6.2 C/C ) mice, but was completely blocked by the SGLT1 inhibitor phlorizin. In Kir6.2 K/K mice, intestinal glucose absorption through SGLT1 was enhanced compared with that in Kir6.2 C/C mice. On the other hand, glucose-induced GIP secretion was enhanced in the diabetic state in Kir6.2 C/C mice. This GIP secretion was partially blocked by phlorizin, but was completely blocked by pretreatment with diazoxide in addition to phlorizin administration. These results demonstrate that glucose-induced GIP secretion depends primarily on SGLT1 in the normal state, whereas the K ATP channel as well as SGLT1 is involved in GIP secretion in the diabetic state in vivo.

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

Cited by 78 publications

References 40 publications

Type 2 Diabetes Impairs Splanchnic Uptake of Glucose but Does Not Alter Intestinal Glucose Absorption During Enteral Glucose Feeding

Type 2 Diabetes Impairs Splanchnic Uptake of Glucose but Does Not Alter Intestinal Glucose Absorption During Enteral Glucose Feeding

Metabolic Adaptations in the Absence of Perilipin

KATP channel as well as SGLT1 participates in GIP secretion in the diabetic state

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