Insulin activation of insulin receptor kinase in erythrocytes is not altered in non-insulin-dependent diabetes and not influenced by hyperglycemia

Klein, HH; Müller, R; Drenckhan, Maren; Schütt, M.; Bätge, Boris; Fehm, H. L.

doi:10.1677/joe.0.1660275

Cited by 3 publications

(2 citation statements)

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“…Insulin receptor kinase and binding activities were measured essentially as described [33,34]. Briefly, 40 µl of solubilized muscle sample were added to microwells coated with anti-insulin receptor antibody for 16 h at 4°C.…”

Section: Methodsmentioning

confidence: 99%

Insulin signalling in skeletal muscle of subjects with or without Type II-diabetes and first degree relatives of patients with the disease

et al. 2002

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Aims/hypothesis. Alterations in insulin signalling could contribute to insulin resistance in Type II (non-insulindependent) diabetes mellitus. Some of these alterations could be secondary to the diabetic state, ie. the hyperglycaemia or increased NEFA concentrations. We sought to exclude such secondary factors and to investigate whether Type II diabetes in itself is associated with altered insulin signalling in skeletal muscle. Methods. Hyperinsulinaemic-euglycaemic clamps were performed in 10 obese Type II diabetic patients whose glucose concentrations had been normalised for 8 h by plasma glucose-adapted insulin infusion, 10 BMImatched first-degree relatives of Type II diabetic patients, and 10 BMI-matched non-diabetic subjects. Muscle biopsies were obtained before and at the end of the clamps, and insulin receptor kinase activity, phosphatidylinositol-3′-kinase activity, Akt-Thr 308 -phosphorylation, and glycogen synthase activity determined. Results. At similar steady-state clamp insulin concentrations (~400 pmol/l) similar receptor kinase activities, phosphatidylinositol-3′-kinase activities, AktThr 308 -phosphorylation, and glycogen synthase activities were found in all subject groups although glucose disposal was reduced in the diabetic subjects and relatives. Pre-clamp signalling levels were different between subject groups, most likely due to different preclamp insulin concentrations. Conclusion/interpretation. Our results in subjects at risk for the development of diabetes and Type II diabetic patients with normalized glucose concentrations suggest that Type II diabetes in itself is not associated with reduced signalling intensity at the studied signalling molecules, at least not at the chosen clamp insulin concentration and under the chosen conditions. Alterations responsible for the reduced glucose disposal could be located downstream of the investigated steps or in alternative insulin signalling pathways. A different spatial organisation of the investigated signalling molecules can also not be excluded. [Diabetologia (2002) Type II (non-insulin-dependent) diabetes mellitus is associated with a reduced insulin-stimulated glucose disposal in skeletal muscle and other tissues [1]. Because insulin resistance is also observed in non-diabetic first-degree relatives of diabetic subjects [2,3,4,5], and because it seems to precede the development of frank diabetes [6], an inherited basis of at least a part of the diabetes-associated insulin resistance has been proposed [7]. On the other hand metabolic abnormalities in the diabetic state itself such as hyper-

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Section: Methodsmentioning

confidence: 99%

Insulin signalling in skeletal muscle of subjects with or without Type II-diabetes and first degree relatives of patients with the disease

et al. 2002

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“…In contrast, insulin had no effect on NHE1 activity of eryhthrocyte from obese individuals . Insulin activation of insulin receptor kinase in erythrocytes is not altered in non-insulin-dependent diabetes and not influenced by hyperglycemia (Klein et al 2000). less in the obese than in the control group.…”

Section: Insulinmentioning

confidence: 76%

Protein Kinases and Protein Phosphatases as Participants in Signal Transduction of Erythrocytes

Maneva¹,

Maneva-Radicheva²

2012

Protein Kinases

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Insulin Sensitivity, Glucose Metabolism, and Membrane Fluidity in Hypertensive Subjects

Tsuda

Nishio

2004

Circulation

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We read with great interest the recent article by Dr Rheaume and colleagues 1 dealing with a possible link between insulin sensitivity and carbohydrate metabolism in hypertensive subjects. The results of their study demonstrated that insulin sensitivity at rest was lower and not improved by exercise in hypertensive subjects. In addition, it was shown that glycogen contents in skeletal muscles were higher with a concomitant increase in total glycogen synthase in hypertensive subjects. The authors proposed that increased intramuscular glycogen storage and resynthesis in hypertension may be related to higher insulin levels and may represent compensatory mechanisms for the reduced insulin sensitivity in this condition.Numerous studies have already shown a relationship between insulin and glucose metabolism. It was demonstrated that metformin, an antihyperglycemic drug that improves insulin sensitivity, acts on the liver to suppress gluconeogenesis by potentiating the effect of insulin. 2 On the other hand, glucose transport across the membranes may be strongly influenced by a variety of membrane functions, such as membrane fluidity. 3 In a study presented earlier, we investigated a relationship between membrane fluidity of erythrocytes and insulin in hypertensive subjects by means of an electron paramagnetic resonance method. 4 The membrane fluidity of erythrocytes was significantly lower in patients with essential hypertension than in normotensive subjects. We showed that the higher the plasma insulin level, the lower the membrane fluidity of erythrocytes. This might indicate that hyperinsulinemia could be involved in the regulation of membrane fluidity of erythrocytes in hypertensive subjects. Wiernsperger 5 proposed that metformin corrects membrane fluidity in the diabetic state and restores the function regulating glucose transport and metabolism. In this context, we speculate that abnormal membrane fluidity associated with hyperinsulinemia might partially explain the increased intramuscular glycogen storage and resynthesis in hypertension. Therefore, we would like to know whether membrane fluidity and other related membrane physicochemical properties of skeletal muscles that the authors biopsied might be changed in hypertensive subjects compared with normotensive controls. It would be necessary to assess more precisely the relationship between membrane functions and insulin-sensitive glucose transport systems in hypertension.

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Insulin activation of insulin receptor kinase in erythrocytes is not altered in non-insulin-dependent diabetes and not influenced by hyperglycemia

Cited by 3 publications

References 33 publications

Insulin signalling in skeletal muscle of subjects with or without Type II-diabetes and first degree relatives of patients with the disease

Insulin signalling in skeletal muscle of subjects with or without Type II-diabetes and first degree relatives of patients with the disease

Protein Kinases and Protein Phosphatases as Participants in Signal Transduction of Erythrocytes

Insulin Sensitivity, Glucose Metabolism, and Membrane Fluidity in Hypertensive Subjects

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