The metabolic clearance of glucose: measurement and meaning

Radziuk, J.; Lickley, H. L. A.

doi:10.1007/bf00283136

Cited by 48 publications

(30 citation statements)

References 53 publications

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“…MCR represents an estimate of glucose utilization, partially corrected for the mass action effect of glucose. The validity and meaning of this measurement have been reviewed (20).…”

mentioning

confidence: 99%

Mechanism of glucoregulatory responses to stress and their deficiency in diabetes.

Miles

Yamatani

Lickley

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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During exercise, increased energy demands are met by increased glucose production that occurs simultaneously with the increased glucose uptake. We had previously observed that, during exercise, metabolic clearance rate of glucose (MCR) increases markedly in normal, but only marginally in poorly controlled diabetic dogs. We wished to determine (i) whether in a more general model of stress matched increases in rate of appearance of glucose and MCR also occur, or if MCR is suppressed, as during catecholamine infusion; and (ii) whether diabetes affects stress-induced changes in rate ofglucose appearance and MCR. Therefore, we injected carbachol (27 nmol/50 pl), an analog of acetylcholine, intracerebroventricularly in seven conscious dogs before and after induction of alloxan diabetes. In normal dogs, plasma epinephrine and cortisol increased 4-to 5-fold, whereas norepinephrine and glucagon doubled. Plasma insulin, however, remained unchanged. Tracer-determined hepatic glucose production increased rapidly, but transiently, by 2.5-fold. This increment can be fully explained by the observed increments in the counterregulatory hormones. Surprisingly, however, MCR also promptly increased, and therefore, plasma glucose changed only marginally. After induction of diabetes, the animals were given intracerebroventricular carbachol while plasma glucose was maintained at moderate hyperglycemia (9.0 ± 0.4 mM). Increments in counterregulatory hormones were similar to those seen in normal dogs, except for exaggerated norepinephrine release. Peripheral insulin levels were higher in diabetic than in normal dogs; however, MCR was markedly reduced and the lipolytic response to stress increased, indicating insulin resistance. Interestingly, the hyperglycemic response to stress was 6-fold greater in diabetic than normal animals, relating mainly to the failure of MCR to rise. Plasma lactate increased equivalently in diabetic and normal animals despite suppression ofMCR in the diabetics, indicating either greater muscle glycogenolysis and/or impairment in glucose oxidation. We conclude that in this stress model MCR increases as in exercise in normal but not in diabetic dogs. We speculate that glucose uptake in stress could be mediated through an insulin-dependent neural mechanism.The obligatory requirement of the brain for glucose necessitates a precise mechanism for glucose homeostasis. The hormonal and metabolic responses to stress have been examined under a variety of stress conditions such as severe injury (1, 2), major surgery (3, 4), myocardial infarction (4, 5), and emotional stress (6); however, the glucoregulatory mechanisms are not fully understood. In exercise, another form of stress, the peripheral energy requirements necessitate changes in glucose metabolism, whereby the augmented rate ofglucose utilization (glucose disappearance; Rd) is precisely matched with an elevated rate of hepatic glucose production (glucose appearance; Ra), thus averting the threat of hypoglycemia (7). There is also a safeguard against hyperg...

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“…MCR represents an estimate of glucose utilization, partially corrected for the mass action effect of glucose. The validity and meaning of this measurement have been reviewed (20).…”

mentioning

confidence: 99%

Mechanism of glucoregulatory responses to stress and their deficiency in diabetes.

Miles

Yamatani

Lickley

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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“…GU was the tracer-determined rate of disappearance (Rd), whereas glucose metabolic clearance rate (MCR) was calculated as Rd/[plasma glucose] (Radziuk & Lickley 1985). Rd corresponded to GU, and plasma clearance rate of glucose to glucose MCR, because plasma glucose levels were below the renal threshold for glucose in dogs (Bjorkman et al 1988).…”

Section: Laboratory Methodsmentioning

confidence: 99%

Direct and indirect effects of insulin on hepatic glucose production in diabetic depancreatized dogs during euglycemia

Gupta¹,

Park²,

Sandhu³

et al. 2006

Journal of Endocrinology

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Insulin suppresses glucose production (GP) via both extrahepatic (indirect) and hepatic (direct) effects. We have shown that the direct effect, undetectable in moderately hyperglycemic diabetic dogs, is restored by insulin-induced euglycemia. The first aim of the present study was to determine whether euglycemia per se, and not the excess insulin needed to obtain it, restores the direct effect of insulin on GP. Basal insulin was given portally in depancreatized dogs to attain only moderate hyperglycemia, then an additional insulin was given portally or peripherally to match the peripheral insulin levels and thus to obtain a greater hepatic insulinization with portal delivery. Plasma glucose was allowed to fall to euglycemia before a euglycemic clamp was performed. During euglycemia, there was a tendency (PZ0$075) for greater suppression of GP by portal than peripheral insulin. Also, there was a significantly different effect of time (PZ0$01) on GP in the two groups, with greater suppression over time in the portal group. The second aim was to test the hypothesis that because of inadequate hepatic insulinization and consequent lack of direct inhibition of GP, peripheral insulin replacement requires peripheral hyperinsulinemia to achieve euglycemia. Portal or peripheral insulin was given to achieve euglycemia and basal GP, and insulin levels were measured. More peripheral insulinemia was required with peripheral than portal insulin replacement to maintain similar euglycemia and GP. Our conclusions are as follows: (1) euglycemia per se is sufficient to acutely restore the direct effect of insulin on GP and (2) at euglycemia, peripheral replacement of insulin, as in insulin-treated diabetes, results in peripheral hyperinsulinemia but unchanged basal GP.

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“…Specifically, hepatic glucose production (HGP) and glucose disposal rate (GDR) were assumed to be equal by 30 min of exercise (see APPENDIX for the validation study). The metabolic clearance rate (MCR) was calculated by normalizing the glucose turnover with the glucose concentration (20). Data are means ± SE.…”

Section: Methodsmentioning

confidence: 99%

“…Blood samples were collected at 20,25,30, and 35 min during exercise for determination of plasma glucose and glucosespecific activity. Glucose concentration (G) and specific activity (SA) were smoothed using the optimal segments program (25) for the purpose of estimating dSA/dt and dG/dt.…”

mentioning

confidence: 99%

Exercise-Stimulated Glucose Turnover in the Rat Is Impaired by Glucosamine Infusion

2001

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The infusion of glucosamine causes insulin resistance, presumably by entering the hexosamine biosynthetic pathway; it has been proposed that this pathway plays a role in hyperglycemia-induced insulin resistance. This study was undertaken to determine if glucosamine infusion could influence exercise-stimulated glucose uptake. Male SD rats were infused with glucosamine at 0.1 mg · kg -1 · min -1 (low-GlcN group), 6.5 mg · kg -1 · min -1 (highGlcN group), or saline (control group) for 6.5 h and exercised on a treadmill for 30 min (17 m/min) at the end of the infusion period. Glucosamine infusion caused a modest increase in basal glycemia in both experimental groups, with no change in tracer-determined basal glucose turnover. During exercise, glucose turnover increased 2.2-fold from 46 ± 2 to 101 ± 5 µmol · kg -1 · min -1 in the control group. Glucose turnover increased to a lesser extent in the glucosamine groups and was limited to 88% of control in the low-GlcN group (47 ± 2 to 90 ± 3 µmol · kg -1 · min -1 ; P < 0.01) and 72% of control in the highGlcN group (43 ± 1 to 73 ± 3 µmol · kg -1 · min -1 ; P < 0.01). Similarly, the metabolic clearance rate (MCR) in the control group increased 72% from 6.1 ± 0.2 to 10.5 ± 0.7 ml · kg -1 · min -1 in response to exercise. However, the increase in MCR was only 83% of control in the low-GlcN group (5.2 ± 0.5 to 8.7 ± 0.5 ml · kg -1 · min -1 ; P < 0.01) and 59% of control in the high-GlcN group (4.5 ± 0.2 to 6.2 ± 0.3 ml · kg -1 · min -1 ; P < 0.01). Neither glucosamine infusion nor exercise significantly affected plasma insulin or free fatty acid (FFA) concentrations. In conclusion, the infusion of glucosamine, which is known to cause insulin resistance, also impaired exercise-induced glucose uptake. This inhibition was independent of hyperglycemia and FFA levels. Diabetes 50:139-142, 2001 C hronic hyperglycemia is the cardinal metabolic feature of diabetes and can adversely affect glucose homeostasis by interfering with insulin action and/or ␤-cell function (1). Studies in humans have shown that experimental hyperglycemia or diabetesassociated hyperglycemia can cause insulin resistance or exacerbate an underlying insulin-resistant state (2). This finding is supported by animal and in vitro studies that directly show that hyperglycemia can cause impaired insulin action in vitro and insulin resistance in vivo (1,3,4).The mechanism by which hyperglycemia causes insulin resistance remains incompletely understood, but several studies have implicated the hexosamine biosynthesis pathway (5-8). This hypothesis holds that hyperglycemia, by way of mass action, leads to increased flux of glucose carbons through the hexosamine pathway (9). This occurs by glutamine:fructose-6-phosphate amidotransferase (GFAT)-mediated conversion of fructose-6-phosphate (F6P) to glucosamine-6-phosphate (G6P), with subsequent metabolism of G6P through the hexosamine pathway. Distal metabolic products of this pathway in some way may lead to decreased insulin-stimulated GLUT4 translocation and subsequent red...

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The metabolic clearance of glucose: measurement and meaning

Cited by 48 publications

References 53 publications

Mechanism of glucoregulatory responses to stress and their deficiency in diabetes.

Mechanism of glucoregulatory responses to stress and their deficiency in diabetes.

Direct and indirect effects of insulin on hepatic glucose production in diabetic depancreatized dogs during euglycemia

Exercise-Stimulated Glucose Turnover in the Rat Is Impaired by Glucosamine Infusion

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