Type I Diabetes is Characterized by Insulin Resistance Not Only with Regard to Glucose, but also to Lipid and Aminoacid Metabolism*

Trevisan, Roberto; Nosadini, R.; Avogaro, Angelo; Lippe, Giovanna; Duner, E.; Fioretto, Paola; Deana, Renzo; Tessari, Paolo; Tiengo, Antonio; Velussi, Mario; Cernigoi, A. M.; Prato, Stefano Del; Crepaldi, Gaetano

doi:10.1210/jcem-62-6-1155

Cited by 48 publications

(18 citation statements)

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“…In accordance with the results of previous reports [31,33], we found that the plasma levels of lactate and pyruvate increased during the hyperinsulinaemic, euglycaemic clamp, indicating an enhanced rate of the overall nonoxidative glucose utilization. While several recent studies [3][4][5] suggest that adipose tissue in humans may be an important source of lactate production in vivo, it is not possible from the present findings to estimate the contribution of lactate derived from subcutaneous fat, since the kinetic pattern of lactate (and pyruvate) in the adipose tissue extracellular space was indistinguishable from that in arterial blood.…”

Section: Discussionsupporting

confidence: 93%

Effect of insulin on human adipose tissue metabolism in situ. Interactions with beta-adrenoceptors

et al. 1992

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Summary. The effects of insulin, and its interactions withcatecholamines through beta-adrenoceptors, on human adipose tissue glucose utilization and lipolysis were investigated in vivo. Microdialysis of the extracellular compartment of abdominal subcutaneous adipose tissue was performed in healthy subjects of normal weight, before and during a 2-h hyperinsulinaemic (61 + 3 mU/1), euglycaemic clamp. The tissue was perfused with or without the beta-adrenergic agonist isoproterenol (10 -6 mol/1), and the tissue dialysate concentrations of glucose, glycerol (lipolysis index) lactate and pyruvate were determined. During the insulin infusion, glucose in adipose tissue decreased by 20 % (p < 0.001), despite arterial steady-state normoglycaemia. The concentrations of lactate and pyruvate increased gradually to a steadystate plateau of twice the basal level in adipose tissue and arterial blood. Insulin-induced suppression of glycerol (lipolysis index) was, if anything, more marked in adipose tissue than in plasma (65 % vs 50 % decrease from baseline levels, p < 0.05). In situ perfusion of adipose tissue with isoproterenol, starting either at the beginning of the study period or at 45 min after initiation of the insulin infusion, resulted in marked and rapid elevations of all the investigated metabolites in the adipose tissue extracellular compartment (p < 0.05-0.005). It is concluded that insulin action on glucose uptake and lipolysis in human adipose tissue in vivo is counteracted by beta-adrenoceptor stimulation. In contrast, insulin and beta-adrenoceptors have synergistic effects on non-oxidative glucose metabolism in human adipose tissue in situ.

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Section: Discussionsupporting

confidence: 93%

Effect of insulin on human adipose tissue metabolism in situ. Interactions with beta-adrenoceptors

et al. 1992

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“…In diabetic patients, hypoglycaemia is mainly associated with absolute hyperinsulinaemia which causes inhibition of ketogenesis and low blood ketone concentrations. In contrast, blood lactate concentration tends to be high in insulin-treated diabetic patients [18], and becomes even higher under conditions of relative hyperinsulinaemia as it occurs, for instance, in the situation of increased physical activity [19] and inadequate insulin dose adjustment.…”

Section: Discussionmentioning

confidence: 97%

Brain function rescue effect of lactate following hypoglycaemia is not an adaptation process in both normal and Type I diabetic subjects

et al. 2000

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Patients with Type I (insulin-dependent) diabetes mellitus receiving intensified insulin therapy and having strict metabolic control are exposed to the risk of recurrent episodes of hypoglycaemia [1]. Defective counterregulatory and symptomatic responses to hypoglycaemia are responsible for reduced awareness of hypoglycaemia [2] which can aggravate cerebral dysfunction by increasing the occurrence and severity Diabetologia (2000) 43: 733±741Brain function rescue effect of lactate following hypoglycaemia is not an adaptation process in both normal and Type I diabetic subjects Abstract Aims/hypothesis. We have previously shown that lactate protects brain function during insulin-induced hypoglycaemia. An adaptation process could, however, not be excluded because the blood lactate increase preceded hypoglycaemia. Methods. We studied seven healthy volunteers and seven patients with Type I (insulin-dependent) diabetes mellitus with a hyperinsulinaemic (1.5 mUḱ g ±1´m in ±1 ) stepwise hypoglycaemic clamp (4.8 to 3.6, 3.0 and 2.8 mmo/l) with and without Na-lactate infusion (30 mmol´kg ±1´m in ±1 ) given after initiation of hypoglycaemic symptoms. Results. The glucose threshold for epinephrine response was similar (control subjects 3.2 0.1 vs 3.2 0.1, diabetic patients = 3.5 0.1 vs 3.5 0.1 mmol/l) in both studies. The magnitude of the response was, however, blunted by lactate infusion (AUC; control subjects 65 28 vs 314 55 nmol/l/180 min, zenith = 2.6 0.5 vs 4.8 0.7 nmol/l, p < 0.05; diabetic patients = 102 14 vs 205 40 nmol/l/180 min, zenith = 1.4 0.4 vs 3.2 0.3 nmol/l, p < 0.01). The glucose threshold for symptoms was also similar (C = autonomic 3.0 0.1 vs 3.0 0.1, neuroglycopenic = 2.8 0.1 vs 2.9 0.1 mmol/l, D = autonomic 3.2 0.1 vs 3.2 0.1, neuroglycopenic 3.1 0.1 vs

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“…Blood was collected into EDTA tubes and rapidly centrifuged at 4°C. The plasma was then stored at -20°C (18). Plasma free fatty acid concentrations were determined by an enzymatic method (19).…”

Section: Methodsmentioning

confidence: 99%

Effects of acute systemic hyperinsulinemia on forearm muscle proteolysis in healthy man.

Tessari¹,

Inchiostro²,

Biolo³

et al. 1991

J. Clin. Invest.

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To investigate the mechanism(s) of insulin-induced suppression of plasma amino acid concentration and release, we studied forearm as well as whole-body leucine and phenylalanine uptake and release during a peripheral insulin infusion in postabsorptive normal subjects using isotope-dilution methods. Before insulin, leucine and phenylalanine release exceeded uptake (P < 0.01 and P < 0.07, respectively). A net output of a-ketoisocaproate (KIC) was also observed. During insulin, arterial plasma leucine, KIC and phenylalanine concentrations decreased (P < 0.05 or less vs. basal), despite ongoing net output of these substrates by the forearm, that persisted after correction for the mean transit time spent through the extracellular muscular space. By the end of insulin, whole-body leucine and phenylalanine concentrations and rate of appearance were decreased (P < 0.01 vs. basal). However, release and uptake of both amino acids by the forearm were not significantly decreased vs. the preinsulin values. These data indicate that systemic hyperinsulinemia acutely decreases plasma amino acid concentrations by acting primarily at sites other than skeletal muscle. (J. Clin. Invest. 1991. 88:27-33.) Key words: amino acid uptake * amino acid release * leucine rate of appearancephenylalanine rate of appearance * net amino acid output Introduction The mechanisms by which insulin influences amino acid as well as protein turnover in vivo have been investigated with isotope dilution techniques in the last years, both in the whole body and at organ level (1-7). While there is a general agreement on the effect ofthe hormone to decrease whole-body rate of appearance (Ra)' of essential amino acids and therefore of

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Type I Diabetes is Characterized by Insulin Resistance Not Only with Regard to Glucose, but also to Lipid and Aminoacid Metabolism*

Cited by 48 publications

References 0 publications

Effect of insulin on human adipose tissue metabolism in situ. Interactions with beta-adrenoceptors

Effect of insulin on human adipose tissue metabolism in situ. Interactions with beta-adrenoceptors

Brain function rescue effect of lactate following hypoglycaemia is not an adaptation process in both normal and Type I diabetic subjects

Effects of acute systemic hyperinsulinemia on forearm muscle proteolysis in healthy man.

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