Neonatal de-afferentation of capsaicin-sensitive sensory nerves increases in vivo insulin sensitivity in conscious adult rats

Koopmans, S.J.; Leighton, Brendan; DeFronzo, Ralph A.

doi:10.1007/s001250050992

Cited by 44 publications

(35 citation statements)

References 33 publications

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“…While the reduced glucose-mediated insulin response in CAP rats might be the result of absence of tonic activation of vagal afferents by gut hormones [17,18], one implication of these findings is that CAP rats are more insulin-sensitive than VEH controls. This idea is in agreement with the findings of Koopmans et al [11], who observed increased whole body insulin action in CAP rats under euglycemic hyperinsulinemic clamp conditions.…”

Section: Discussionsupporting

confidence: 94%

“…Although we have not performed a full analysis of plasma corticosterone levels over the course of the IVGTT, it might be possible that this reduced plasma corticosterone level underlies the increased insulin sensitivity in CAP rats. A lower corticosterone response in CAP rats was previously observed by Koopmans et al [11], and, together with the data in the present study, this suggests a role for vagal afferents and/or sensory nerves in the activation of the HPA axis during hyperglycemia. It seems likely that vagal afferents normally convey stimulatory actions of gut hormones, such as CCK, on HPA axis activity [24].…”

Section: Discussionsupporting

confidence: 91%

“…Furthermore, deafferentated animals have a long-term decrease in white adipose tissue mass [9] and are more resistant to ageing-associated obesity [10]. Finally, CAP treatment results in increased whole body insulin sensitivity [11] and a lower degree of ageing-associated insulin resistance [10]. These observations indicate that CAP-treated animals are able, or even have improved capability, to maintain body weight and energy homeostasis, despite the fact that they lack seemingly important information transmitted via vagal afferents to the CNS.…”

Section: Introductionmentioning

confidence: 99%

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Neonatal capsaicin causes compensatory adjustments to energy homeostasis in rats

Wall

Wielinga

Strubbe

et al. 2006

Physiology & Behavior

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Several mechanisms involved in ingestive behavior and neuroendocrine activity rely on vagal afferent neuronal signaling. Seemingly contradictory to this idea are observations that vagal afferent neuronal ablation by neonatal capsaicin (CAP) treatment has relatively small effects on glucose homeostasis and long-term regulation of energy balance. It may be proposed that humoral endocrine factors and/or their sensitivities compensate for the loss of vagal afferent information, particularly when subjects face disturbances in ambient fuel levels. Therefore, male adult rats neonatally treated with CAP or with the vehicle (VEH) underwent intravenous glucose tolerance tests (IVGTTs) during which blood fuel levels, and circulating adipose, pancreatic, and adrenal hormones were assessed. CAP rats displayed similar hyperglycemia as VEH rats, but with markedly reduced plasma insulin and corticosterone responses. These results indicate that CAP rats have increased insulin sensitivity during hyperglycemic episodes, and lower plasma levels of corticosterone in CAP rats relative to VEH rats could underlie this effect. After the IVGTT, CAP rats had increased plasma adiponectin and reduced plasma resistin levels, and these alterations in adipose hormones might be relevant for post-ingestive metabolic processes. In a second experiment, anorexigenic efficacies of cholecystokinin and leptin were assessed. While VEH rats, but not CAP rats, responded with reduced food intake to i.p. injected cholecystokinin, only CAP rats responded to i.v. infused leptin with a reduction in food intake. It is concluded that reduced HPA axis activity and/or increased leptin signaling could underlie compensations in fuel handling and energy balance following CAP treatment.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Neonatal capsaicin causes compensatory adjustments to energy homeostasis in rats

Wall

Wielinga

Strubbe

et al. 2006

Physiology & Behavior

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“…This could be explained as a consequence of the potentiated insulin secretion but also by an increased insulin action because a similar increased elimination was found in streptozotocin diabetic rats [109]. The glucose disposal during recent euglycaemic, hyperinsulinaemic clamp studies was also increased in capsaicin-treated rats [110]. These results imply that the peripheral action of insulin is likewise dependent on intact sensory nerves, which is supported by in vitro studies showing that CGRP reduces the action of insulin [111].…”

Section: Sensory Nervesmentioning

confidence: 61%

Autonomic regulation of islet hormone secretion - Implications for health and disease

2000

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“…Animal studies suggest that capsaicin-sensitive sensory neurons play a role in the regulation of glucose tolerance and insulin sensitivity (66). These findings suggest that defective neurogenic vasodilation, in addition to its pathophysiological role in causing complications, could be responsible for as much as 25% of impaired insulin sensitivity (67,68). Avogaro et al (69) and others question its significance.…”

Section: Vinik and Associatesmentioning

confidence: 99%

Dermal Neurovascular Dysfunction in Type 2 Diabetes

et al. 2001

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OBJECTIVE -To review evidence for a relationship between dermal neurovascular dysfunction and other components of the metabolic syndrome of type 2 diabetes.RESEARCH DESIGN AND METHODS -We review and present data supporting concepts relating dermal neurovascular function to prediabetes and the metabolic syndrome. Skin blood flow can be easily measured by laser Doppler techniques.RESULTS -Heat and gravity have been shown to have specific neural, nitrergic, and independent mediators to regulate skin blood flow. We describe data showing that this new tool identifies dermal neurovascular dysfunction in the majority of type 2 diabetic patients. The defect in skin vasodilation is detectable before the development of diabetes and is partially correctable with insulin sensitizers. This defect is associated with C-fiber dysfunction (i.e., the dermal neurovascular unit) and coexists with variables of the insulin resistance syndrome. The defect most likely results from an imbalance among the endogenous vasodilator compound nitric oxide, the vasodilator neuropeptides substance P and calcitonin gene-related peptide, and the vasoconstrictors angiotensin II and endothelin. Hypertension per se increases skin vasodilation and does not impair the responses to gravity, which is opposite to that of diabetes, suggesting that the effects of diabetes override and counteract those of hypertension.CONCLUSIONS -These observations suggest that dermal neurovascular function is largely regulated by peripheral C-fiber neurons and that dysregulation may be a component of the metabolic syndrome associated with type 2 diabetes. Diabetes Care 24:1468 -1475, 2001A number of functional disturbances are found in the dermal microvasculature of diabetic subjects. These include decreased microvascular blood flow (1), increased vascular resistance (2), decreased tissue PO 2 (3), and altered vascular permeability characteristics, such as loss of the anionic charge barrier and decreased charge selectivity. Decreased microvascular blood flow and increased vascular resistance in diabetes could result from alterations in dermal neurovascular function, such as impaired dilator responses to substance P, calcitonin gene-related peptide (CGRP), and reactivity to nociceptive stimulation. Diabetes also disrupts vasomotion-the rhythmic contraction exhibited by arterioles and small arteries (4,5). Unmyelinated C-fibers, which constitute the central reflex pathway, are assumed to be damaged in diabetic neuropathy, contributing to abnormalities in cutaneous blood flow (6). Warm thermal sensation is a functional measure of C-fibers in the periphery, and the impairment of this function was paralleled by a reduction of vasomotion. These findings support an interaction between small unmyelinated C-fiber function and vasomotion, although it is not clear whether the neurological deficit precedes or follows the loss of baseline vascular response. A clear relationship between skin microvascular insufficiency and neuropathy has not yet been established. It is possible that ski...

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Neonatal de-afferentation of capsaicin-sensitive sensory nerves increases in vivo insulin sensitivity in conscious adult rats

Cited by 44 publications

References 33 publications

Neonatal capsaicin causes compensatory adjustments to energy homeostasis in rats

Neonatal capsaicin causes compensatory adjustments to energy homeostasis in rats

Autonomic regulation of islet hormone secretion - Implications for health and disease

Dermal Neurovascular Dysfunction in Type 2 Diabetes

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