Olfactory marker protein regulation of glucagon secretion in hyperglycemia

Ju Hun Oh; Ye Eon Han; Ya Ru Bao; Chan Woo Kang; Jae Hyung Koo; Cheol Ryong Ku; Yoon Hee Cho; Eun Jig Lee

doi:10.1038/s12276-022-00843-8

Olfactory marker protein regulation of glucagon secretion in hyperglycemia

Ju Hun Oh, Ye Eon Han, Ya Ru Bao, Chan Woo Kang, Jae Hyung Koo, Cheol Ryong Ku, Yoon Hee Cho, Eun Jig Lee

Department of Internal Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

The olfactory marker protein (OMP), which is also expressed in nonolfactory tissues, plays a role in regulating the kinetics and termination of olfactory transduction. Thus, we hypothesized that OMP may play a similar role in modulating the secretion of hormones involved in Ca²⁺ and cAMP signaling, such as glucagon. In the present study, we confirmed nonolfactory α-cell-specific OMP expression in human and mouse pancreatic islets as well as in the murine α-cell line αTC1.9. Glucagon and OMP expression increased under hyperglycemic conditions. Omp knockdown in hyperglycemic αTC1.9 cells using small-interfering RNA (siRNA) reduced the responses to glucagon release and the related signaling pathways compared with the si-negative control. The OMP^lox/lox;GCG^cre/w mice expressed basal glucagon levels similar to those in the wild-type OMP^lox/lox mice but showed resistance against streptozotocin-induced hyperglycemia. The ectopic olfactory signaling events in pancreatic α-cells suggest that olfactory receptor pathways could be therapeutic targets for reducing excessive glucagon levels.

Original language	English
Pages (from-to)	1502-1510
Number of pages	9
Journal	Experimental and Molecular Medicine
Volume	54
Issue number	9
DOIs	https://doi.org/10.1038/s12276-022-00843-8
Publication status	Published - 2022 Sept

Bibliographical note

Funding Information:
We acknowledge Dr. Pedro Luis Herrera, Geneva University, Switzerland for providing glucagon Cre-mice for our studies. This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, South Korea (grant number: HR18C0012) and by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (grant number: 2020R1I1A1A01074357).

Publisher Copyright:
© 2022, The Author(s).

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Medicine
Molecular Biology
Clinical Biochemistry

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title = "Olfactory marker protein regulation of glucagon secretion in hyperglycemia",

abstract = "The olfactory marker protein (OMP), which is also expressed in nonolfactory tissues, plays a role in regulating the kinetics and termination of olfactory transduction. Thus, we hypothesized that OMP may play a similar role in modulating the secretion of hormones involved in Ca2+ and cAMP signaling, such as glucagon. In the present study, we confirmed nonolfactory α-cell-specific OMP expression in human and mouse pancreatic islets as well as in the murine α-cell line αTC1.9. Glucagon and OMP expression increased under hyperglycemic conditions. Omp knockdown in hyperglycemic αTC1.9 cells using small-interfering RNA (siRNA) reduced the responses to glucagon release and the related signaling pathways compared with the si-negative control. The OMPlox/lox;GCGcre/w mice expressed basal glucagon levels similar to those in the wild-type OMPlox/lox mice but showed resistance against streptozotocin-induced hyperglycemia. The ectopic olfactory signaling events in pancreatic α-cells suggest that olfactory receptor pathways could be therapeutic targets for reducing excessive glucagon levels.",

author = "Oh, {Ju Hun} and Han, {Ye Eon} and Bao, {Ya Ru} and Kang, {Chan Woo} and Koo, {Jae Hyung} and Ku, {Cheol Ryong} and Cho, {Yoon Hee} and Lee, {Eun Jig}",

note = "Funding Information: We acknowledge Dr. Pedro Luis Herrera, Geneva University, Switzerland for providing glucagon Cre-mice for our studies. This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, South Korea (grant number: HR18C0012) and by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (grant number: 2020R1I1A1A01074357). Publisher Copyright: {\textcopyright} 2022, The Author(s).",

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AU - Ku, Cheol Ryong

AU - Cho, Yoon Hee

AU - Lee, Eun Jig

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Olfactory marker protein regulation of glucagon secretion in hyperglycemia

Abstract

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