The effect of norepinephrine on insulin secretion and glucose effectiveness in non—insulin-dependent diabetes

Walters, John; Ward, Gerald M.; Barton, Jackson Clayborn; Arackal, R.; Boston, Raymond C.; Best, James D.; Alford, F. P.

doi:10.1016/s0026-0495(97)90146-3

Cited by 31 publications

(23 citation statements)

References 31 publications

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“…by Jellinger and Riederer (42) of raised indoleamine concentrations in postmortem brains of patients with diabetic coma suggests that brain transmitter metabolism may be altered in acidotic condition. On the other hand, glucose tolerance was significantly decreased during NA infusion as compared with saline control as well as NIDDM patients (33). Many other studies showed uncontrolled hyperglycemia ravages cerebral microvessels and it can be susceptible to blood brain barrier (34)(35)(36)(37).…”

Section: Discussionmentioning

confidence: 96%

An Experimental Analysis of the Catecholamines in Hyperglycemia and Acidosis-Induced Rat Brain

Ramakrishnan

Nazer²,

Suthanthirarajan

et al. 2003

Int J Immunopathol Pharmacol

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Hyperglycemia and acidosis are the hallmarks of diabetes. Since these factors play an important role in diabetic complications, we have studied the brain catecholamine levels in hyperglycemic and acidotic conditions per se, Experimentally induced hyperglycemia and acidosis are accompanied by significant alterations in the catecholamine levels in discrete areas of the brain. We and others have shown that chronic or acute diabetes in animals, as well as in humans results in altered neurotransmitter levels. In the present study, hyperglycemia maintained by daily external administration of glucose for thirty days showed increased level of dopamine in striatum and hippocampus, elevation of norepinephrine in hippocampus, and increased level of epinephrine in hypothalamus, midbrain and pons medulla. The ammonium chloride induced acidosis demonstrated significant elevation of dopamine in midbrain and significant increase of norepinephrine in hypothalamus and midbrain, and increased level of epinephrine in hypothalamus, pons medulla and cerebral cortex. On the other hand, sodium acetoacetate induced acidosis did not show any significant change in the level of catecholamines in any of the areas studied. In conclusion, the changes in catecholamine levels observed in experimentally induced hyperglycemic as well as in acidotic conditions are closely related to the changes observed in spontaneous or alloxan or streptozotocin diabetic animals, thereby suggesting that these conditions may be responsible for the changes observed in diabetic animals.Hyperglycemia and acidosis are the key factors which lead to diabetic complications through multifaceted events. Chronic diabetes is associated with characteristic functional and structural abnormalities in the eyes, kidneys, nerves and arteries, which become clinically apparent only after many years of disease (1,2). Acute administration of glucose suppresses the discharge rate of dopamine-containing substantia nigra neurons in chloral hydrate anesthetized rats (3). Glucose also activates tyrosine hydroxylase in rat striatal synaptosomes (4), which would tend to increase the rate of dopamine synthesis and release. On the other hand, the infusion of epinephrine induces reduction in glucose disposal (5). There are several other reports suggesting that not only a turnover rate, but also a steady state level of monoamines may be altered in diabetes (6,7).Numerous studies have shown that the experimentally induced diabetes in animal models have demonstrated abnormalities in noradrenergic as well as dopaminergic systems, including the turnover rate (8,9), density of receptors (10,11) and other functions that depend on norepinephrine (NA) or dopamine (DA) systems (12)(13)(14). Catecholamines and hormones are important organizers of the brain, especially during the development of neuroendocirne systems (15,16).

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Section: Discussionmentioning

confidence: 96%

An Experimental Analysis of the Catecholamines in Hyperglycemia and Acidosis-Induced Rat Brain

Ramakrishnan

Nazer²,

Suthanthirarajan

et al. 2003

Int J Immunopathol Pharmacol

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“…This link is also apparent in other syndromes associated with NE excess, e.g., pheochromocytoma (Skyler 2000) and may involve several peripheral NE's effects including: (1) enhancement of hepatic glucose output (Brodows et al 1975;); (2) interference with the normal feedback control exerted by circulating glucose on pancreatic islets secreting insulin and glucagon (Havel et al 1988); (3) diminution of insulin receptors' sensitivity (Walters et al 1997); (4) suppressive action on insulin secretion (Matsunaga et al 1989); and (5) reduction of glucose uptake by skeletal muscles due to NE-induced vasoconstriction (Esler et al 2001).…”

Section: Discussionmentioning

confidence: 96%

Effects of pharmacological doses of 2-deoxyglucose on plasma catecholamines and glucose levels in patients with schizophrenia

Elman

Rott²,

Green

et al. 2004

Psychopharmacology

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“…In addition, peripheral effects of NE alone could be hypothesized to contribute to potential adverse outcomes. For instance, given preclinical (Nagai et al 1995) and clinical (Walters et al 1997) evidence suggesting NE's anti-insulin activity, this effect may be involved in the development of diabetic ketoacidosis reported during treatment with both atypical agents (Colli et al 1999;Croarkin et al 2000).…”

Section: Discussionmentioning

confidence: 99%

Effects of Risperidone on the Peripheral Noradrenegic System in Patients with Schizophrenia A Comparison with Clozapine and Placebo

Elman

Goldstein

Green

et al. 2002

Neuropsychopharmacology

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Risperidone is an atypical antipsychotic drug that increases plasma norepinephrine (NE) levels, but the mechanism behind this effect is unclear. We measured arterial plasma levels of NE and other catechols during intravenous infusion of tritium-labeled NE ( 3 H-NE) in risperidone-Clozapine is an atypical antipsychotic drug (APD) with efficacy superior to that of conventional agents and with little or no extrapyramidal signs or symptoms (EPS) (Kane et al. 1988;Lieberman et al. 1989;Breier et al. 1994a;Meltzer 1995;Meltzer et al. 1996). Because these advantageous therapeutic properties are accompanied by unusually severe side effects, scientists have been searching for clozapine-like APDs that would share its beneficial features but not induce bone marrow toxicity, seizures, or hypotension. This search has resulted in the introduction of four "newer atypical APDs" (i.e., risperidone, olanzapine, quetiapine, and ziprasidone), all of which have important effects on both dopaminergic and serotonergic neurotransmitter systems. Because none of these compounds has been proven as efficacious as the prototype, clozapine, in the treatment of resistant cases, continued research is focusing on other neurotransmitter systems affected by clozapine.Clozapine profoundly increases norepinephrine (NE) levels in both CSF (Ackenheil 1989;Lieberman et al. 1989;Lieberman et al. 1991;Pickar et al. 1992) and plasma (Pickar et al. 1992;Green et al. 1993;Davidson et al. 1993;Breier 1994;Breier et al. 1994b;Schulz et al. 1996;Schulz et al. 1997;Brown et al. 1997;Fleischhaker et al. 1998;Elman et al. 1999), an effect not seen with typical APDs. In some (Breier et al. 1994b;Schulz et al. 1997;Fleischhaker et al. 1998), but not all (Brown et al. 1997) studies, plasma NE increases have been related to clinical improvement, suggesting that this pharmacological effect may play a role in clozapine's beneficial central actions. In this context, findings implicating noradrenergic dysregulation in the pathophysiology of schizophrenia (Stein and Wise 1971;Sternberg 1984;Breier et al. 1990;Rao and Moller 1994;Breier 1994;Yamamoto et al. 1994;Litman et al. 1996;Breier et al. 1998;Goff and Evins 1998;Friedman et al. 1999a;Friedman et al. 1999b;Klimek et al. 1999) further support inquiry into the relevance of noradrenergic mechanisms in the action of APDs.We have reported previous data suggesting that high plasma NE levels in clozapine-treated patients result from increases in the appearance rate of the endogenously released NE in the plasma (spillover) rather than from decreased neuronal uptake of NE, inhibition of intraneuronal monoamine oxidase (MAO), or adrenoceptor antagonism . Risperidone, the next atypical antipsychotic drug marketed in the United States after clozapine, is associated with a low incidence of EPS and may have improved efficacy compared with conventional agents (Kane and McGlashan 1995;Pickar 1995;Campbell et al. 1999). Interestingly, risperidone has also recently been observed in a clinical study to produce a modest (i.e., 58%) inc...

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The effect of norepinephrine on insulin secretion and glucose effectiveness in non—insulin-dependent diabetes

Cited by 31 publications

References 31 publications

An Experimental Analysis of the Catecholamines in Hyperglycemia and Acidosis-Induced Rat Brain

An Experimental Analysis of the Catecholamines in Hyperglycemia and Acidosis-Induced Rat Brain

Effects of pharmacological doses of 2-deoxyglucose on plasma catecholamines and glucose levels in patients with schizophrenia

Effects of Risperidone on the Peripheral Noradrenegic System in Patients with Schizophrenia A Comparison with Clozapine and Placebo

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