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Reversion of aging-related DHEAS decline in mouse plasma alleviates aging-related glucose tolerance impairment by potentiation of glucose-stimulated insulin secretion of acute phase.
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- Author(s): Ma J;Ma J; Yue J; Yue J; Huang R; Huang R; Liao Y; Liao Y; Li S; Li S; Liu W; Liu W
- Source:
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2018 Jun 07; Vol. 500 (3), pp. 671-675.- Publication Type:
Journal Article; Research Support, Non-U.S. Gov't- Language:
English - Source:
- Additional Information
- Source: Publisher: Elsevier Country of Publication: United States NLM ID: 0372516 Publication Model: Print Cited Medium: Internet ISSN: 1090-2104 (Electronic) Linking ISSN: 0006291X NLM ISO Abbreviation: Biochem Biophys Res Commun Subsets: MEDLINE
- Publication Information: Publication: <2002- >: San Diego, CA : Elsevier
Original Publication: New York, Academic Press. - Subject Terms:
- Abstract: Aims/hypothesis: The latest research proposes mild age-related diabetes (MARD) as a subgroup of type 2 diabetes. While in human circulating dehydroepiandrosterone sulfate (DHEAS) decline with age is related to MARD, the role of circulating DHEAS in insulin secretion remains little known.
Methods: After intraperitoneal administration of glucose (2 g/kg) together with DHEAS (50 μg/kg) or equivalent DMSO to young (6-8 week old) or aging (12 month old) male C57BL/6 mice, plasma DHEAS and blood glucose were measured at indicated time point. Then in vitro, we investigated DHEAS effects on GSIS of acute phase in aging mice pancreatic islets as well as in MIN6 cells. Finally we conducted pharmacological studies in MIN6 cells to examine whether exert its effects on insulin secretion by itself.
Results: We found in vivo that aging mice had lower plasma DHEAS levels and impaired glucose tolerence compared to young mice and that the aged mice but not the young mice receiving DHEAS supplement had improved glucose tolerance as soon as 15 min after glucose injection compared to the ones with DMSO administration. These results indicate that in male mice, aging-related DHEAS decline in plasma contribute to aging-related impairment of glucose tolerence and that reversion of aging-related DHEAS deficiency in aging mice plasma could alleviate aging-related glucose tolerance impairment. Consistently, in vitro DHEAS glucose-and dose-dependently potentiated glucose-stimulated insulin secretion (GSIS) of acute phase in both aging male mice pancreatic islets and MIN6 cells. Moreover, none of steroid sulfatase (STS) inhibitor STX64 (10 nM), androgen receptor (AR) blocker flutamide (1 mM) or estrogen receptor (ER) antagonist ICI182780 (1 mM), affected DHEAS-potentiated high GSIS of acute phase indicating this potentiation exercised by DHEAS per se CONCLUSIONS: /interpretation These results lead us to tentatively conclude that aging-related DHEAS decline may imply MARD development and that adequate DHEAS supplement may be a precise medicine and preventive measure for MARD.
(Copyright © 2018. Published by Elsevier Inc.) - Contributed Indexing: Keywords: Circulating concentration; Dehydroepiandrosterone sulfate (DHEAS); Insulin secretion of acute phase; Mild age-related diabetes (MARD); Mouse
- Accession Number: 0 (Insulin)
57B09Q7FJR (Dehydroepiandrosterone Sulfate)
IY9XDZ35W2 (Glucose) - Publication Date: Date Created: 20180422 Date Completed: 20180914 Latest Revision: 20181217
- Publication Date: 20221213
- Accession Number: 10.1016/j.bbrc.2018.04.134
- Accession Number: 29678582
- Source:
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