Pathophysiology and Pharmacological Treatment of Insulin Resistance

Matthaei, S.

doi:10.1210/er.21.6.585

Cited by 183 publications

(153 citation statements)

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“…Type 2 diabetes is one of the most common chronic diseases, affecting about 150 million people world wide [1]. It is characterised by insulin resistance of peripheral tissues such as liver, muscle, and fat which cannot be overcome by hypersecretion of pancreatic beta cells [2].…”

Section: Adipocytokines-emerging Regulators Of Insulin Sensitivitymentioning

confidence: 99%

Regulation of adipocytokines and insulin resistance

2003

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It has long been known that obesity and insulin resistance are linked. Recently, it has been shown that adipocytes secrete several proteins including tumour necrosis factor-α, interleukin-6, resistin, and adiponectin. Since several of these so-called adipocytokines influence insulin sensitivity and glucose metabolism profoundly, they might provide a molecular link between increased adiposity and impaired insulin sensitivity. Thiazolidinediones which decrease insulin resistance and are used in the treatment of Type 2 diabetes seem to mediate part of their insulin-sensitising effects via modulation of adipocytokine expression.Furthermore, hormones such as β-adrenergic agonists, insulin, glucocorticoids, and growth hormone might impair insulin sensitivity at least in part via up-regulation or down-regulation of adipocytokine synthesis. We summarise the current knowledge on how major adipocyte-secreted proteins are regulated by hormones and drugs influencing insulin sensitivity and discuss its implications for insulin resistance and obesity. [Diabetologia (2003[Diabetologia ( ) 46:1594[Diabetologia ( -1603

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Section: Adipocytokines-emerging Regulators Of Insulin Sensitivitymentioning

confidence: 99%

Regulation of adipocytokines and insulin resistance

2003

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“…Impaired insulin action occurs at the level of all insulin-dependent tissues: liver, muscle and adipose tissue. These abnormalities are likely the consequence of molecular defects at the level of postreceptor signalling, glucose transport, and/or regulatory enzymes of intracellular glucose metabolism [18]. 2.…”

Section: Early-phase Insulin Secretion and Glucose Homeostasismentioning

confidence: 99%

Loss of early insulin secretion leads to postprandial hyperglycaemia

2003

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Aims/Hypothesis. A loss of early-phase insulin response is common in Type 2 diabetic patients and in people with impaired glucose metabolism. It is hypothesized that this alteration is not simply a marker for the risk of developing diabetes, rather it is a an important pathogenetic mechanism causing excessive postprandial hyperglycaemia. Methods. Relevant literature on the epidemiology, physiopathology, and therapeutic intervention related to loss of early insulin secretion and postprandial hyperglycaemia has been analysed. Results. In response to intravenous glucose, insulin secretion is biphasic. This behaviour translates as a rapid release of insulin into the blood stream in response to the ingestion of carbohydrates or a mixed meal. The rapid increase in portal insulin concentration and the avid binding of the hormone to its receptor on liver cell membranes, account for a prompt suppression of endogenous glucose production and reduction of the rate of increase in plasma glucose concentrations. This has been supported by experimental studies carried out in both animals and humans: the selective abolition of early insulin secretion in healthy subjects results in impaired glucose tolerance, excessive glucose excursions, and possible hampering of the thermic effects of ingested carbohydrates. In nondiabetic subjects, the loss of early insulin secretion is a determinant for developing diabetes. The critical role of the early-phase insulin response in determining postprandial hyperglycaemia, is supported by an amelioration of glucose tolerance by restoring the acute rise in plasma insulin concentrations after the ingestion of both glucose and a mixed meal. This amelioration in plasma glucose profile can prevent late hyperglycaemia and hyperinsulinaemia. Conclusion/interpretation. Therapeutic approaches aimed at restoring a physiological pattern of insulin secretion could prove effective in reducing postprandial glucose excursions particularly in the early stage of Type 2 diabetes. [Diabetologia (2003)

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“…Free fatty acids, which are often elevated in type 2 diabetes (Kruszynska et al, 1997), and tumor-necrosis-factoralpha (TNF-alpha), which is secreted by 'full' adipocytes (Hotamisligil et al, 1995), are known to inhibit insulin action, possibly by inhibition of insulin receptor function (phosphorylation of serine and threonine residues; Matthaei et al, 2000), or by post-receptor events leading to inhibition of GLUT-4 activity. It is of importance to note that these disturbances also occur in obesity without diabetes.…”

Section: Insulin Resistancementioning

confidence: 99%

“…Indeed, insulin action has been shown to vary between families (Martin et al, 1992). So far, few mutations in susceptibility genes have been found (Matthaei et al, 2000). Since obesity itself is under marked genetic control (Bouchard, 1996;Stunkard et al, 1986), and since it leads to insulin resistance, this might explain that many type 2 diabetic subjects are obese and insulin resistant, and that this occurs in families.…”

Section: Insulin Resistancementioning

confidence: 99%

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Early disturbances in insulin secretion in the development of type 2 diabetes mellitus

Haeften

2002

Molecular and Cellular Endocrinology

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After a short description of normal glucose homeostasis, recent findings in relation to insulin release in three groups with a high risk of future development of type 2 diabetes are described. Hyperglycemic clamps in subjects with impaired glucose tolerance (IGT) clearly indicate that pancreatic beta cell function is decreased, in addition to the decreased insulin sensitivity. In women with former gestational diabetes mellitus (GDM), insulin release is also lower than in controls. In Caucasian first-degree relatives (FDRs) with normal glucose tolerance, various studies have shown that beta cell function is lower than in controls, while on the average insulin sensitivity is normal. This implies that beta cell function is disturbed earlier in subjects at risk of developing diabetes than is often appreciated. In the near future, the genetic studies currently underway will presumably unravel the pathogenesis of disturbances both in insulin secretion and in insulin action, in type 2 diabetes mellitus. #

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Pathophysiology and Pharmacological Treatment of Insulin Resistance

Cited by 183 publications

References 0 publications

Regulation of adipocytokines and insulin resistance

Regulation of adipocytokines and insulin resistance

Loss of early insulin secretion leads to postprandial hyperglycaemia

Early disturbances in insulin secretion in the development of type 2 diabetes mellitus

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