7 Diabetes and adrenal disease

Nestler, John E.; McClanahan, Mark A.

doi:10.1016/s0950-351x(05)80169-7

Cited by 37 publications

(21 citation statements)

References 73 publications

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“…These pathways have been demonstrated in other species, including man. Pheochromocytoma has been attributed as a cause for non-insulin-dependent diabetes mellitus and diabetic patients suffer from increased catecholamine release (39,40). These pathways are therefore important targets for antidiabetic drugs (41).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of insulin secretion via distinct signaling pathways in alpha2-adrenoceptor knockout mice

Peterhoff

Sieg²,

Brede³

et al. 2003

European Journal of Endocrinology

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Objective: Adrenaline inhibits insulin secretion through activation of a 2 -adrenoceptors (ARs). These receptors are linked to pertussis toxin-sensitive G proteins. Agonist binding leads to inhibition of adenylyl cyclase, inhibition of Ca 2þ channels and activation of K þ channels. Recently, three distinct subtypes of a 2 -AR were described, a 2A -AR, a 2B -AR and a 2C -AR. At present, it is unknown which of these a 2 -AR subtype(s) may regulate insulin secretion. We used mice deficient in a 2 -ARs to analyze the coupling and role of individual a 2 -AR subtypes in insulin-secreting b cells. Methods: The inhibitory effect of adrenaline on insulin secretion was measured in freshly isolated and cultured wild type (wt) and a 2 -AR knockout (KO) mouse islets in order to examine the receptor subtypes which mediate adrenaline-induced inhibition of insulin secretion. Adenylyl cyclase activity was measured in isolated cultured islets. Membrane potential was measured using the amphotericin B permeabilized patch clamp method in isolated and cultured single islet cells. Results: In wt, a 2A -and a 2C -AR KO mouse islets, adrenaline, 1 mmol/l, inhibited secretion by 83, 80 and 100% respectively. In contrast, in a 2A/2C -AR double KO mouse islets, adrenaline had no effect on stimulated secretion indicating that both a 2A -AR and a 2C -AR, but not a 2B -AR, are functionally expressed in mouse islets. Surprisingly, glucose (16.7 mmol/l)-induced secretion in the presence of 1 mmol/l forskolin was greatly impaired in a 2A -AR KO islets. However, when cAMP levels were increased further by the combination of forskolin (5 mmol/l) and 3-isobutyl-1-methylxanthine (100 mmol/l), secretion was stimulated 2.7-fold (8.5-fold in wt islets). Adrenaline lowered the concentration of cAMP in wt and a 2C -AR KO mouse islets by 74%. Adrenaline also hyperpolarized wt and a 2C -AR KO b cells. In contrast, adrenaline did not inhibit adenylyl cyclase in islets of a 2A -AR KO mice, nor did it hyperpolarize a 2A -AR KO b cells. Conclusion: Adrenaline inhibits insulin release through a 2A -and a 2C -ARs via distinct intracellular signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Inhibition of insulin secretion via distinct signaling pathways in alpha2-adrenoceptor knockout mice

Peterhoff

Sieg²,

Brede³

et al. 2003

European Journal of Endocrinology

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“…In the few cases of primary aldosteronism where metabolic dysfunction is severe and clinical diabetes mellitus occurs, the course of the diabetes differs from that seen in patients with type 2 diabetes not due to secondary adrenal causes [16]. First, the glucose intolerance associated with primary aldosteronism is milder.…”

Section: Primary Aldosteronism and Diabetes Mellitusmentioning

confidence: 98%

The effect of aldosterone on glucose metabolism

Corry

Tuck²

2003

Current Science Inc

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There is an association of glucose intolerance and diabetes with primary aldosteronism, but the frequency and mechanisms are not clear. This paper reviews the possible mechanisms of impaired glucose metabolism in primary aldosteronism. Patients with primary aldosteronism can have impaired pancreatic insulin release and reduction in insulin sensitivity. These effects may be due to hypokalemia, but the evidence suggests other factors such as a direct impact of excess aldosterone on insulin action in contributing to the metabolic dysfunction. In general adrenal surgery in cases of aldosterone-producing adenoma will correct the metabolic abnormalities, but it is less sure if treatment with spironolactone in cases of idiopathic hyperplasia will correct impaired glucose tolerance.

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“…Adrenal disorders characterized by increased secretion of adrenocortical or adrenomedullary hormones such as hyperaldosteronism, Cushing's syndrome, hyperandrogenism, and pheochromocytoma have been associated with various metabolic disorders, including impaired glucose tolerance, IR, and overt diabetes [58]. These abnormalities constitute the end result of the adverse effects of adrenal hormones on various components of insulin action and glucose metabolism.…”

Section: Muscle Insulin Resistance and Endocrine Diseasementioning

confidence: 99%

Skeletal Muscle Insulin Resistance in Endocrine Disease

Peppa

Koliaki

Nikolopoulos

et al. 2010

Journal of Biomedicine and Biotechnology

100

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We summarize the existing literature data concerning the involvement of skeletal muscle (SM) in whole body glucose homeostasis and the contribution of SM insulin resistance (IR) to the metabolic derangements observed in several endocrine disorders, including polycystic ovary syndrome (PCOS), adrenal disorders and thyroid function abnormalities. IR in PCOS is associated with a unique postbinding defect in insulin receptor signaling in general and in SM in particular, due to a complex interaction between genetic and environmental factors. Adrenal hormone excess is also associated with disrupted insulin action in peripheral tissues, such as SM. Furthermore, both hyper- and hypothyroidism are thought to be insulin resistant states, due to insulin receptor and postreceptor defects. Further studies are definitely needed in order to unravel the underlying pathogenetic mechanisms. In summary, the principal mechanisms involved in muscle IR in the endocrine diseases reviewed herein include abnormal phosphorylation of insulin signaling proteins, altered muscle fiber composition, reduced transcapillary insulin delivery, decreased glycogen synthesis, and impaired mitochondrial oxidative metabolism.

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7 Diabetes and adrenal disease

Cited by 37 publications

References 73 publications

Inhibition of insulin secretion via distinct signaling pathways in alpha2-adrenoceptor knockout mice

Inhibition of insulin secretion via distinct signaling pathways in alpha2-adrenoceptor knockout mice

The effect of aldosterone on glucose metabolism

Skeletal Muscle Insulin Resistance in Endocrine Disease

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