Absorption and disposition of a glucose load in the conscious dog

Abumrad, Naji N.; Cherrington, Alan D.; Williams, P. E. V.; Lacy, William W.; Rabin, David

doi:10.1152/ajpendo.1982.242.6.e398

Cited by 87 publications

(82 citation statements)

References 15 publications

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“…Using the transonic flow sensors we noted that a rise in plasma glucose produced a small increase in blood flow from the intestine (Abumrad et al, 1982), but there was no effect of metformin (250 mg kg-') on blood flow in the HPV or lower abdominal IVC under conditions of basal or raised glycaemia.…”

Section: Discussionmentioning

confidence: 90%

Importance of the intestine as a site of metformin‐stimulated glucose utilization

Bailey¹,

Mynett

Page

1994

British J Pharmacology

126

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1 The intestine has been implicated as a site of increased glucose utilization by the antihyperglycaemic drug, metformin. This study makes a quantitative assessment of this effect. 2 Glucose utilization by the intestine and hind limb region was determined by arterial-venous glucose difference adjusted for blood flow rate in fasted rats receiving a hyperglycaemic hyperinsulinaemic infusion. 3 Intrajejunal administration of metformin, 250 mg kg-', increased glucose disposal during the infusion procedure, associated with increased glucose utilization in the intestine by 69% and in the hind limb region by 40%. 4 Metformin, 250mgkg'1, increased glucose disappearance during an intravenous glucose tolerance test. This was accompanied by increased uptake of tritiated 2-deoxy-D-glucose into the intestinal mucosa to a greater extent than into skeletal muscles (per unit wet weight of tissue). 5 The results demonstrate that the intestinal mucosa is a quantitatively important site of increased glucose utilization during the blood glucose-lowering effect of metformin.

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Section: Discussionmentioning

confidence: 90%

Importance of the intestine as a site of metformin‐stimulated glucose utilization

Bailey¹,

Mynett

Page

1994

British J Pharmacology

126

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“…In subjects with normal hepatic insulin sensitivity, the rise in plasma glucose and insulin (20,21) concentrations is sufficient to suppress EGP and ameliorate the rise in plasma glucose concentration. On the other hand, in hepatic insulin-resistant individuals, an even greater rise in plasma glucose and insulin concentrations causes only a small to moderate suppression of EGP, and this results in a greater increase in plasma glucose concentration during the early phase (0 -30 min) of the OGTT.…”

Section: Calculationsmentioning

confidence: 99%

Muscle and Liver Insulin Resistance Indexes Derived From the Oral Glucose Tolerance Test

Abdul‐Ghani¹,

et al. 2007

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OBJECTIVE -To derive indexes for muscle and hepatic insulin sensitivity from the measurement of plasma glucose and insulin concentrations during an oral glucose tolerance test (OGTT). RESEARCH DESIGN AND METHODS-A total of 155 subjects of Mexican-American origin (58 male and 97 female, aged 18 -70 years, BMI 20 -65 kg/m 2 ) with normal glucose tolerance (n ϭ 100) or impaired glucose tolerance (n ϭ 55) were studied. Each subject received a 75-g OGTT and a euglycemic insulin clamp in combination with tritiated glucose. The OGTTderived indexes of muscle and hepatic insulin sensitivity were compared with hepatic and muscle insulin sensitivity, which was directly measured with the insulin clamp, by correlation analysis.RESULTS -The product of total area under curve (AUC) for glucose and insulin during the first 30 min of the OGTT (glucose 0 -30 [AUC] ϫ insulin 0 -30 [AUC]) strongly correlated with the hepatic insulin resistance index (fasting plasma insulin ϫ basal endogenous glucose production) (r ϭ 0.64, P Ͻ 0.0001). The rate of decay of plasma glucose concentration from its peak value to its nadir during the OGTT divided by the mean plasma insulin concentration (dG/dt Ϭ I) strongly correlated with muscle insulin sensitivity measured with the insulin clamp (P ϭ 0.78, P Ͻ 0.0001).CONCLUSIONS -Novel estimates for hepatic and muscle insulin resistance from OGTT data are presented for quantitation of insulin sensitivity in nondiabetic subjects. Diabetes Care 30:89 -94, 2007S keletal muscle and hepatic insulin resistance are characteristic features in type 2 diabetes (1). Insulin resistance is also commonly observed in nondiabetic subjects who are overweight and is associated with a cluster of metabolic and cardiovascular risk factors (dyslipidemia, hypertension, visceral obesity, and elevated inflammatory markers) known as the insulin resistance syndrome or dysmetabolic syndrome (2). Individuals with the insulin resistance syndrome have an approximate threefold increased risk for coronary heart disease and type 2 diabetes (3). Their risk for cardiovascular and allcause mortality is also increased compared with insulin-sensitive individuals (3). It is estimated that in the year 2000, more than one-third of the adult population (Ͼ20 years of age) in the U.S. had the insulin resistance syndrome and therefore are at high risk for the development of type 2 diabetes and cardiovascular disease (4).Improved insulin sensitivity with lifestyle intervention, e.g., weight reduction and increased physical activity, lowers the risk of future type 2 diabetes in insulinresistant individuals by more than onehalf (5,6), reduces the prevalence of cardiovascular risk factors (7), and decreases cardiovascular morbidity and mortality (8). Pharmacological intervention with agents that improve insulin sensitivity, including thiazolidinediones and metformin, also reduces the risk of conversion from impaired glucose tolerance (IGT) to type 2 diabetes (5,9) and decreases the risk of cardiovascular disease in individuals with established type 2 ...

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“…Such gradients have been measured directly in animals in response to an intragastric glucose load. Intragastric administration of glucose to animals causes an immediate increase in portal vein glucose concentration, greater than that shown in the systemic arterial circulation, creating a positive portal arterial glucose concentration gradient [35,36,37] which can last for up to 60 min and is then lost as the glucose concentration in the portal vein falls [38]. In our study we can assume that the U 13 C 6 glucose appears in the systemic circulation slightly later than any appearance of glucose in the portal system, indicating a positive portal arterial glucose concentration gradient at the time of inducing hypoglycaemia as the tracer levels in the circulation are increasing.…”

Section: Discussionmentioning

confidence: 98%

The role of hepatic portal glucose sensing in modulating responses to hypoglycaemia in man

et al. 2002

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Aims/hypothesis. The role of glucose sensing cells in the human hepatic portal system in the initiation of the neuroendocrine responses to acute hypoglycaemia is not known. We investigated the effect of raising blood glucose concentrations in the hepatic-portal vein on neurohumoral responses during induction of systemic hypoglycaemia in nine healthy male volunteers. Methods. Each subject received an insulin infusion (3 mU·kg -1 ·min -1 ) on two occasions, in random order. Variable rate glucose infusion was used to maintain plasma glucose at 5 mmol/l for 60 min, then 3.2 mmol/l for 60 min. At 20 min prior to hypoglycaemia, subjects drank 20 g of glucose in water or water sweetened with saccharin. In five of the volunteers, the oral glucose was labelled with U-13C6 glucose, which showed peak systemic glucose absorption between 90 and 110 min. Five volunteers also repeated the study with a euglycaemic clamp.Results. Oral glucose was associated with a reduction in the early adrenaline response to hypoglycaemia, the area under the curve from 90 to 110 min falling from 24.02±20.84 (means ± SD) to 15. vere hypoglycaemia during the pharmacological treatment of diabetes mellitus. The inability to generate or detect the warning symptoms of early hypoglycaemia puts diabetic patients at high risk of episodes of severe hypoglycaemia [1] and often the fear of hypoglycaemia limits the optimisation of glycaemic control [2]. Associated with loss of subjective awareness of hypoglycaemia is a lowering of the glucose concentration required to initiate the counterregulatory response to hypoglycaemia, as well as a reduction in the magnitude and intensity of the counterregulatory response at any given blood glucose concentration [3,4,5]. The speculation that these defects are principally the result of defective glucose sensing gains support from data showing similar changes in the neuroendocrine rePerception of a minor decrease in plasma glucose concentration and initiation of a counterregulatory response are essential factors in the defence against se-

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Absorption and disposition of a glucose load in the conscious dog

Cited by 87 publications

References 15 publications

Importance of the intestine as a site of metformin‐stimulated glucose utilization

Importance of the intestine as a site of metformin‐stimulated glucose utilization

Muscle and Liver Insulin Resistance Indexes Derived From the Oral Glucose Tolerance Test

The role of hepatic portal glucose sensing in modulating responses to hypoglycaemia in man

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