Peripheral mechanisms mediating the sustained antidiabetic action of FGF1 in the brain

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Peripheral mechanisms mediating the sustained antidiabetic action of FGF1 in the brain. / Scarlett, Jarrad M.; Muta, Kenjiro; Brown, Jenny M.; Rojas, Jennifer M.; Matsen, Miles E.; Acharya, Nikhil K.; Secher, Anna; Ingvorsen, Camilla; Jorgensen, Rasmus; Høeg-Jensen, Thomas; Stefanovski, Darko; Bergman, Richard N.; Piccinini, Francesca; Kaiyala, Karl J.; Shiota, Masakazu; Morton, Gregory J.; Schwartz, Michael W.

In: Diabetes, Vol. 68, No. 3, 01.03.2019, p. 654-664.

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

Harvard

Scarlett, JM, Muta, K, Brown, JM, Rojas, JM, Matsen, ME, Acharya, NK, Secher, A, Ingvorsen, C, Jorgensen, R, Høeg-Jensen, T, Stefanovski, D, Bergman, RN, Piccinini, F, Kaiyala, KJ, Shiota, M, Morton, GJ & Schwartz, MW 2019, 'Peripheral mechanisms mediating the sustained antidiabetic action of FGF1 in the brain', Diabetes, vol. 68, no. 3, pp. 654-664. https://doi.org/10.2337/db18-0498

APA

Scarlett, J. M., Muta, K., Brown, J. M., Rojas, J. M., Matsen, M. E., Acharya, N. K., Secher, A., Ingvorsen, C., Jorgensen, R., Høeg-Jensen, T., Stefanovski, D., Bergman, R. N., Piccinini, F., Kaiyala, K. J., Shiota, M., Morton, G. J., & Schwartz, M. W. (2019). Peripheral mechanisms mediating the sustained antidiabetic action of FGF1 in the brain. Diabetes, 68(3), 654-664. https://doi.org/10.2337/db18-0498

Vancouver

Scarlett JM, Muta K, Brown JM, Rojas JM, Matsen ME, Acharya NK et al. Peripheral mechanisms mediating the sustained antidiabetic action of FGF1 in the brain. Diabetes. 2019 Mar 1;68(3):654-664. https://doi.org/10.2337/db18-0498

Author

Scarlett, Jarrad M. ; Muta, Kenjiro ; Brown, Jenny M. ; Rojas, Jennifer M. ; Matsen, Miles E. ; Acharya, Nikhil K. ; Secher, Anna ; Ingvorsen, Camilla ; Jorgensen, Rasmus ; Høeg-Jensen, Thomas ; Stefanovski, Darko ; Bergman, Richard N. ; Piccinini, Francesca ; Kaiyala, Karl J. ; Shiota, Masakazu ; Morton, Gregory J. ; Schwartz, Michael W. / Peripheral mechanisms mediating the sustained antidiabetic action of FGF1 in the brain. In: Diabetes. 2019 ; Vol. 68, No. 3. pp. 654-664.

Bibtex

@article{17a41d1eac8040b7b91e9649e1aaba99,
title = "Peripheral mechanisms mediating the sustained antidiabetic action of FGF1 in the brain",
abstract = "We recently reported that in rodent models of type 2 diabetes (T2D), a single intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1) induces remission of hyperglycemia that is sustained for weeks. To clarify the peripheral mechanisms underlying this effect, we used the Zucker diabetic fatty fa/fa rat model of T2D, which, like human T2D, is characterized by progressive deterioration of pancreatic b-cell function after hyperglycemia onset. We report that although icv FGF1 injection delays the onset of b-cell dysfunction in these animals, it has no effect on either glucose-induced insulin secretion or insulin sensitivity. These observations suggest that FGF1 acts in the brain to stimulate insulin-independent glucose clearance. On the basis of our finding that icv FGF1 treatment increases hepatic glucokinase gene expression, we considered the possibility that increased hepatic glucose uptake (HGU) contributes to the insulin-independent glucose-lowering effect of icv FGF1. Consistent with this possibility, we report that icv FGF1 injection increases liver glucokinase activity by approximately twofold. We conclude that sustained remission of hyperglycemia induced by the central action of FGF1 involves both preservation of b-cell function and stimulation of HGU through increased hepatic glucokinase activity.",
author = "Scarlett, {Jarrad M.} and Kenjiro Muta and Brown, {Jenny M.} and Rojas, {Jennifer M.} and Matsen, {Miles E.} and Acharya, {Nikhil K.} and Anna Secher and Camilla Ingvorsen and Rasmus Jorgensen and Thomas H{\o}eg-Jensen and Darko Stefanovski and Bergman, {Richard N.} and Francesca Piccinini and Kaiyala, {Karl J.} and Masakazu Shiota and Morton, {Gregory J.} and Schwartz, {Michael W.}",
year = "2019",
month = mar,
day = "1",
doi = "10.2337/db18-0498",
language = "English",
volume = "68",
pages = "654--664",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association",
number = "3",

}

RIS

TY - JOUR

T1 - Peripheral mechanisms mediating the sustained antidiabetic action of FGF1 in the brain

AU - Scarlett, Jarrad M.

AU - Muta, Kenjiro

AU - Brown, Jenny M.

AU - Rojas, Jennifer M.

AU - Matsen, Miles E.

AU - Acharya, Nikhil K.

AU - Secher, Anna

AU - Ingvorsen, Camilla

AU - Jorgensen, Rasmus

AU - Høeg-Jensen, Thomas

AU - Stefanovski, Darko

AU - Bergman, Richard N.

AU - Piccinini, Francesca

AU - Kaiyala, Karl J.

AU - Shiota, Masakazu

AU - Morton, Gregory J.

AU - Schwartz, Michael W.

PY - 2019/3/1

Y1 - 2019/3/1

N2 - We recently reported that in rodent models of type 2 diabetes (T2D), a single intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1) induces remission of hyperglycemia that is sustained for weeks. To clarify the peripheral mechanisms underlying this effect, we used the Zucker diabetic fatty fa/fa rat model of T2D, which, like human T2D, is characterized by progressive deterioration of pancreatic b-cell function after hyperglycemia onset. We report that although icv FGF1 injection delays the onset of b-cell dysfunction in these animals, it has no effect on either glucose-induced insulin secretion or insulin sensitivity. These observations suggest that FGF1 acts in the brain to stimulate insulin-independent glucose clearance. On the basis of our finding that icv FGF1 treatment increases hepatic glucokinase gene expression, we considered the possibility that increased hepatic glucose uptake (HGU) contributes to the insulin-independent glucose-lowering effect of icv FGF1. Consistent with this possibility, we report that icv FGF1 injection increases liver glucokinase activity by approximately twofold. We conclude that sustained remission of hyperglycemia induced by the central action of FGF1 involves both preservation of b-cell function and stimulation of HGU through increased hepatic glucokinase activity.

AB - We recently reported that in rodent models of type 2 diabetes (T2D), a single intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1) induces remission of hyperglycemia that is sustained for weeks. To clarify the peripheral mechanisms underlying this effect, we used the Zucker diabetic fatty fa/fa rat model of T2D, which, like human T2D, is characterized by progressive deterioration of pancreatic b-cell function after hyperglycemia onset. We report that although icv FGF1 injection delays the onset of b-cell dysfunction in these animals, it has no effect on either glucose-induced insulin secretion or insulin sensitivity. These observations suggest that FGF1 acts in the brain to stimulate insulin-independent glucose clearance. On the basis of our finding that icv FGF1 treatment increases hepatic glucokinase gene expression, we considered the possibility that increased hepatic glucose uptake (HGU) contributes to the insulin-independent glucose-lowering effect of icv FGF1. Consistent with this possibility, we report that icv FGF1 injection increases liver glucokinase activity by approximately twofold. We conclude that sustained remission of hyperglycemia induced by the central action of FGF1 involves both preservation of b-cell function and stimulation of HGU through increased hepatic glucokinase activity.

UR - https://www.mendeley.com/catalogue/cc6cf084-0343-3e09-8fb5-6186707a916d/

U2 - 10.2337/db18-0498

DO - 10.2337/db18-0498

M3 - Journal article

C2 - 30523024

VL - 68

SP - 654

EP - 664

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 3

ER -

ID: 261001409