Differential effects of insulin therapy on hepatic and peripheral insulin sensitivity in Type 2 (non-insulin-dependent) diabetes

Nankervis, Alison; Proietto, Joseph; Aitken, P.; Harewood, M.; Alford, F.

doi:10.1007/bf00253737

Cited by 61 publications

(44 citation statements)

References 36 publications

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“…In other words, it has been, perhaps tacitly, assumed that the MCR of glucose is directly proportional to plasma insulin concentrations and independent of glucose concentrations, [e.g. [43][44][45][46][47]. The observation was made however both in man [48][49][50] and in the dog [51], that the relationship between the rate of glucose utilization, Rd, and glucose concentrations at a fixed insulin level, although linear, did not pass through the origin.…”

Section: The Relationships Of Mcr To Insulin and Glucosementioning

confidence: 99%

The metabolic clearance of glucose: measurement and meaning

Radziuk

Lickley

1985

Diabetologia

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Section: The Relationships Of Mcr To Insulin and Glucosementioning

confidence: 99%

The metabolic clearance of glucose: measurement and meaning

Radziuk

Lickley

1985

Diabetologia

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“…In the short term, during insulin infusions the liver has been found to be more sensitive to increasing insulin levels than the periphery (1)(2)(3)(4), suggesting that it is the initial site at which glycemia may be regulated. Evidence as to relative efficiency of portal and peripheral delivery of insulin in the regulation of both glucose and other aspects of metabolism is not entirely consistent.…”

Section: Introductionmentioning

confidence: 99%

The effect of systemic venous drainage of the pancreas on insulin sensitivity in dogs.

Radziuk

Barron²,

Najm³

et al. 1993

J. Clin. Invest.

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To assess the metabolic consequences of the diversion of the pancreatic venous drainage to the systemic circulation, the pancreaticoduodenal and gastrosplenic veins were anastomosed to the inferior vena cava in nine normal dogs. This procedure maintained the integrity of the entire pancreas while shunting the hormonal output ofthe pancreas to the periphery. The metabolic effects were assessed from the sensitivity to insulin during a euglycemic hyperinsulinemic glucose clamp using an insulin infusion of 800 IAU/kg per min. The studies were controlled by their duplication in seven dogs identically treated but with the pancreatic veins reanastomosed to the portal vein. No differences in systemic insulin levels or insulin sensitivity before and after surgery were seen under these circumstances. After diversion, however, basal insulin levels rose from 4.5±1.0 to 11.5±2.5 gU/ml. Basal glucose metabolic clearance rate (MCR) rose to 3.0±0.4 from 2.0±0.3 ml/kg per min. On insulin infusion, maximal stimulation of MCR within the 2-h infusion period was to 15.2±2.5 ml/kg per min preoperatively and to 7.2±0.8 ml/kg per min after diversion. Using ratios of MCR-to-insulin concentration as an index of insulin sensitivity, it was demonstrated that this index decreased by at least 50% after diversion. These data imply that portal venous drainage of the pancreas is an important factor in the determination of peripheral insulin sensitivity. (J. Clin. Invest. 92:1713-1721

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“…Poorly controlled Type 1 (26,54), Type 2 (27,47), and experimentally induced (3,23) diabetes are characterized by chronic hyperglycemia, absolute and/or relative hypoinsulinemia, raised hepatic glucose production (HGP), elevated circulating FFA and glucagon levels, and severe insulin resistance, particularly in SkM (48,54). Moreover, in response to acute mild to moderate exercise (ϳ40 -60% V O 2 max ), suboptimally controlled hypoinsulinemic diabetic subjects exhibit metabolic abnormalities, including reduced exercise-stimulated Rd tissue [Rd tissue (ex)] and oxidation rates from both plasma glucose and SkM glycogen (29,34,57), and increased exercise-stimulated oxidation rates from both plasma FFA and SkM fat (34,51).…”

mentioning

confidence: 99%

Prevailing hyperglycemia is critical in the regulation of glucose metabolism during exercise in poorly controlled alloxan-diabetic dogs

Christopher¹,

Rantzau²,

McConell³

et al. 2005

Journal of Applied Physiology

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. Prevailing hyperglycemia is critical in the regulation of glucose metabolism during exercise in poorly controlled alloxan-diabetic dogs. J Appl Physiol 98: 930 -939, 2005; doi:10.1152/japplphysiol.00687.2004.-The separate impacts of the chronic diabetic state and the prevailing hyperglycemia on plasma substrates and hormones, in vivo glucose turnover, and ex vivo skeletal muscle (SkM) during exercise were examined in the same six dogs before alloxan-induced diabetes (prealloxan) and after 4 -5 wk of poorly controlled hyperglycemic diabetes (HGD) in the absence and presence of ϳ300-min phlorizin-induced (glycosuria mediated) normoglycemia (NGD). For each treatment state, the ϳ15-h-fasted dog underwent a primed continuous 150-min infusion of [3-3 H]glucose, followed by a 30-min treadmill exercise test (ϳ65% maximal oxygen capacity), with SkM biopsies taken from the thigh (vastus lateralis) before and after exercise. In the HGD and NGD states, preexercise hepatic glucose production rose by 130 and 160%, and the metabolic clearance rate of glucose (MCRg) fell by 70 and 37%, respectively, compared with the corresponding prealloxan state, but the rates of glucose uptake into peripheral tissues (Rdtissue) and total glycolysis (GF) were unchanged, despite an increased availability of plasma free fatty acid in the NGD state. Exercise-induced increments in hepatic glucose production, Rdtissue, and plasma-derived GF were severely blunted by ϳ30 -50% in the NGD state, but increments in MCRg remained markedly reduced by ϳ70 -75% in both diabetic states. SkM intracellular glucose concentrations were significantly elevated only in the HGD state. Although Rdtissue during exercise in the diabetic states correlated positively with preexercise plasma glucose and insulin and GF and negatively with preexercise plasma free fatty acid, stepwise regression analysis revealed that an individual's preexercise glucose and GF accounted for 88% of Rdtissue during exercise. In conclusion, the prevailing hyperglycemia in poorly controlled diabetes is critical in maintaining a sufficient supply of plasma glucose for SkM glucose uptake during exercise. During phlorizin-induced NGD, increments in both Rdtissue and GF are impaired due to a diminished fuel supply from plasma glucose and a sustained reduction in increments of MCRg. glucose uptake; plasma-derived glycolysis; skeletal muscle; free fatty acids; metabolic clearance rate of glucose; phlorizin-induced normoglycemia THE REGULATION OF GLUCOSE METABOLISM in skeletal muscle (SkM) during exercise occurs predominantly via an insulinindependent pathway (13,16,22) and involves the recruitment of SkM GLUT4 transporters from a distinct insulin-independent GLUT-4 pool (13). It is known that the prior insulin sensitivity of an individual is important in determining the rate of glucose uptake into SkM (Rd tissue ) in response to acute exercise (28). Furthermore, the intensity and duration of the exercise are also critical in determining the relative importance of carbohydrate and fat substrates as ...

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Differential effects of insulin therapy on hepatic and peripheral insulin sensitivity in Type 2 (non-insulin-dependent) diabetes

Cited by 61 publications

References 36 publications

The metabolic clearance of glucose: measurement and meaning

The metabolic clearance of glucose: measurement and meaning

The effect of systemic venous drainage of the pancreas on insulin sensitivity in dogs.

Prevailing hyperglycemia is critical in the regulation of glucose metabolism during exercise in poorly controlled alloxan-diabetic dogs

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