Sensory nerve desensitization by resiniferatoxin improves glucose tolerance and increases insulin secretion in Zucker Diabetic Fatty rats and is associated with reduced plasma activity of dipeptidyl peptidase IV.

Dorte X Gram; Anker J Hansen; Carolyn F Deacon; Christian L Brand; Ulla Ribel; Michael Wilken; Richard D Carr; Ove Svendsen; Bo Ahrén

doi:10.1016/j.ejphar.2004.12.039

Sensory nerve desensitization by resiniferatoxin improves glucose tolerance and increases insulin secretion in Zucker Diabetic Fatty rats and is associated with reduced plasma activity of dipeptidyl peptidase IV.

Dorte X Gram, Anker J Hansen, Carolyn F Deacon, Christian L Brand, Ulla Ribel, Michael Wilken, Richard D Carr, Ove Svendsen, Bo Ahrén

Department of Biomedical Sciences

41 Citations (Scopus)

Abstract

Sensory nerve desensitization by capsaicin has been shown to improve the diabetic condition in Zucker Diabetic Fatty rats. However, administration of capsaicin to adult rats is associated with an increased mortality. Therefore, in this experiment, we examined the influence of resiniferatoxin, a tolerable analogue of capsaicin suitable for in vivo use, on the diabetic condition of Zucker Diabetic Fatty rats. A single subcutaneous injection of resiniferatoxin (0.01 mg/kg) to these rats was tolerable, with no mortality. When administered to early diabetic rats at 15 weeks of age, the further deterioration of glucose homeostasis was prevented by resiniferatoxin. Further, when administered to overtly diabetic rats at 19 weeks of age, resiniferatoxin markedly improved glucose tolerance at two weeks after administration and this was accompanied by an increased insulin response to oral glucose as well as a reduction in the plasma levels of dipeptidyl peptidase IV. Therefore, resiniferatoxin is a safe alternative to capsaicin for further investigations of the role of the sensory nerves in experimental diabetes.

Original language	English
Journal	European Journal of Pharmacology
Volume	509
Issue number	2-3
Pages (from-to)	211-7
Number of pages	6
ISSN	0014-2999
DOIs	https://doi.org/10.1016/j.ejphar.2004.12.039
Publication status	Published - 2005

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Gram, D. X., Hansen, A. J., Deacon, C. F., Brand, C. L., Ribel, U., Wilken, M., Carr, R. D., Svendsen, O., & Ahrén, B. (2005). Sensory nerve desensitization by resiniferatoxin improves glucose tolerance and increases insulin secretion in Zucker Diabetic Fatty rats and is associated with reduced plasma activity of dipeptidyl peptidase IV. European Journal of Pharmacology, 509(2-3), 211-7. https://doi.org/10.1016/j.ejphar.2004.12.039

Sensory nerve desensitization by resiniferatoxin improves glucose tolerance and increases insulin secretion in Zucker Diabetic Fatty rats and is associated with reduced plasma activity of dipeptidyl peptidase IV. / Gram, Dorte X; Hansen, Anker J; Deacon, Carolyn F et al.

In: European Journal of Pharmacology, Vol. 509, No. 2-3, 2005, p. 211-7.

Research output: Contribution to journal › Journal article › Research › peer-review

Gram, DX, Hansen, AJ, Deacon, CF, Brand, CL, Ribel, U, Wilken, M, Carr, RD, Svendsen, O & Ahrén, B 2005, 'Sensory nerve desensitization by resiniferatoxin improves glucose tolerance and increases insulin secretion in Zucker Diabetic Fatty rats and is associated with reduced plasma activity of dipeptidyl peptidase IV.', European Journal of Pharmacology, vol. 509, no. 2-3, pp. 211-7. https://doi.org/10.1016/j.ejphar.2004.12.039

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title = "Sensory nerve desensitization by resiniferatoxin improves glucose tolerance and increases insulin secretion in Zucker Diabetic Fatty rats and is associated with reduced plasma activity of dipeptidyl peptidase IV.",

abstract = "Sensory nerve desensitization by capsaicin has been shown to improve the diabetic condition in Zucker Diabetic Fatty rats. However, administration of capsaicin to adult rats is associated with an increased mortality. Therefore, in this experiment, we examined the influence of resiniferatoxin, a tolerable analogue of capsaicin suitable for in vivo use, on the diabetic condition of Zucker Diabetic Fatty rats. A single subcutaneous injection of resiniferatoxin (0.01 mg/kg) to these rats was tolerable, with no mortality. When administered to early diabetic rats at 15 weeks of age, the further deterioration of glucose homeostasis was prevented by resiniferatoxin. Further, when administered to overtly diabetic rats at 19 weeks of age, resiniferatoxin markedly improved glucose tolerance at two weeks after administration and this was accompanied by an increased insulin response to oral glucose as well as a reduction in the plasma levels of dipeptidyl peptidase IV. Therefore, resiniferatoxin is a safe alternative to capsaicin for further investigations of the role of the sensory nerves in experimental diabetes.",

author = "Gram, {Dorte X} and Hansen, {Anker J} and Deacon, {Carolyn F} and Brand, {Christian L} and Ulla Ribel and Michael Wilken and Carr, {Richard D} and Ove Svendsen and Bo Ahr{\'e}n",

note = "Keywords: Animals; Antigens, CD26; Area Under Curve; Blood Glucose; Diabetes Mellitus, Type 2; Diterpenes; Glucose; Glucose Tolerance Test; Insulin; Neurons, Afferent; Obesity; Rats; Rats, Zucker; Time Factors",

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doi = "10.1016/j.ejphar.2004.12.039",

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T1 - Sensory nerve desensitization by resiniferatoxin improves glucose tolerance and increases insulin secretion in Zucker Diabetic Fatty rats and is associated with reduced plasma activity of dipeptidyl peptidase IV.

AU - Gram, Dorte X

AU - Hansen, Anker J

AU - Deacon, Carolyn F

AU - Brand, Christian L

AU - Ribel, Ulla

AU - Wilken, Michael

AU - Carr, Richard D

AU - Svendsen, Ove

AU - Ahrén, Bo

N1 - Keywords: Animals; Antigens, CD26; Area Under Curve; Blood Glucose; Diabetes Mellitus, Type 2; Diterpenes; Glucose; Glucose Tolerance Test; Insulin; Neurons, Afferent; Obesity; Rats; Rats, Zucker; Time Factors

PY - 2005

Y1 - 2005

N2 - Sensory nerve desensitization by capsaicin has been shown to improve the diabetic condition in Zucker Diabetic Fatty rats. However, administration of capsaicin to adult rats is associated with an increased mortality. Therefore, in this experiment, we examined the influence of resiniferatoxin, a tolerable analogue of capsaicin suitable for in vivo use, on the diabetic condition of Zucker Diabetic Fatty rats. A single subcutaneous injection of resiniferatoxin (0.01 mg/kg) to these rats was tolerable, with no mortality. When administered to early diabetic rats at 15 weeks of age, the further deterioration of glucose homeostasis was prevented by resiniferatoxin. Further, when administered to overtly diabetic rats at 19 weeks of age, resiniferatoxin markedly improved glucose tolerance at two weeks after administration and this was accompanied by an increased insulin response to oral glucose as well as a reduction in the plasma levels of dipeptidyl peptidase IV. Therefore, resiniferatoxin is a safe alternative to capsaicin for further investigations of the role of the sensory nerves in experimental diabetes.

AB - Sensory nerve desensitization by capsaicin has been shown to improve the diabetic condition in Zucker Diabetic Fatty rats. However, administration of capsaicin to adult rats is associated with an increased mortality. Therefore, in this experiment, we examined the influence of resiniferatoxin, a tolerable analogue of capsaicin suitable for in vivo use, on the diabetic condition of Zucker Diabetic Fatty rats. A single subcutaneous injection of resiniferatoxin (0.01 mg/kg) to these rats was tolerable, with no mortality. When administered to early diabetic rats at 15 weeks of age, the further deterioration of glucose homeostasis was prevented by resiniferatoxin. Further, when administered to overtly diabetic rats at 19 weeks of age, resiniferatoxin markedly improved glucose tolerance at two weeks after administration and this was accompanied by an increased insulin response to oral glucose as well as a reduction in the plasma levels of dipeptidyl peptidase IV. Therefore, resiniferatoxin is a safe alternative to capsaicin for further investigations of the role of the sensory nerves in experimental diabetes.

U2 - 10.1016/j.ejphar.2004.12.039

DO - 10.1016/j.ejphar.2004.12.039

M3 - Journal article

C2 - 15733558

SN - 0014-2999

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SP - 211

EP - 217

JO - European Journal of Pharmacology

JF - European Journal of Pharmacology

IS - 2-3

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