Glucose-dependent insulinotropic polypeptide reduces fat-specific expression and activity of 11[beta]-hydroxysteroid dehydrogenase type 1 and inhibits release of free fatty acids.(ORIGINAL ARTICLE)
Glucose-dependent insulinotropic polypeptide (GIP) has been suggested to have direct effects on nonislet tissues. GIP also reportedly increased glucose uptake and inhibition of lipolysis in adipocytes after inhibition of the intracellular cortisone-cortisol shuttle 11[beta]-hydroxysteroid dehydrogen...
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| Veröffentlicht in: | Diabetes (New York, N.Y.) N.Y.), 2012-02, Vol.61 (2), p.292 |
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| creator | Gogebakan, Ozlem Andres, Janin Biedasek, Katrin Mai, Knut Kuhnen, Peter Krude, Heiko Isken, Frank Rudovich, Natalia Osterhoff, Martin A Kintscher, Ulrich Nauck, Michael Pfeiffer, Andreas F.H Spranger, Joachim |
| description | Glucose-dependent insulinotropic polypeptide (GIP) has been suggested to have direct effects on nonislet tissues. GIP also reportedly increased glucose uptake and inhibition of lipolysis in adipocytes after inhibition of the intracellular cortisone-cortisol shuttle 11[beta]-hydroxysteroid dehydrogenase type 1 (11[beta]-HSD1). We here analyzed whether GIP modifies lipid metabolism and further elucidated the relation between GIP, 11[beta]-HSD1, and fatty acid metabolism. GIP reduced activity of 11[beta]-HSD1 promoter constructs and the expression and activity of 11[beta]-HSD1 in differentiated 3T3-L1 adipocytes in a time- and dose-dependent fashion. This was paralleled by a reduction of free fatty acid (FFA) release and a reduced expression of key enzymes regulating lipolysis in adipose tissue. Preinhibition of 11[beta]-HSD1 completely abolished GIP-induced effects on FFA release. To investigate the acute effects of GIP in humans, a randomized clinical trial was performed. GIP lowered circulating FFAs compared with saline control and reduced expression and ex vivo activity of 11[beta]-HSD1 and adipose triglyceride lipase expression in subcutaneous fat biopsies. Our data suggest that GIP reduces FFA release from adipose tissue by inhibition of lipolysis or by increased reesterification. This process appears to depend on a modification of 11[beta]-HSD1 activity. In general, the presented data support that GIP has direct and insulin-independent effects on adipose tissue. Diabetes 61:292-300, 2012 |
| doi_str_mv | 10.2337/db10-0902 |
| format | Article |
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GIP also reportedly increased glucose uptake and inhibition of lipolysis in adipocytes after inhibition of the intracellular cortisone-cortisol shuttle 11[beta]-hydroxysteroid dehydrogenase type 1 (11[beta]-HSD1). We here analyzed whether GIP modifies lipid metabolism and further elucidated the relation between GIP, 11[beta]-HSD1, and fatty acid metabolism. GIP reduced activity of 11[beta]-HSD1 promoter constructs and the expression and activity of 11[beta]-HSD1 in differentiated 3T3-L1 adipocytes in a time- and dose-dependent fashion. This was paralleled by a reduction of free fatty acid (FFA) release and a reduced expression of key enzymes regulating lipolysis in adipose tissue. Preinhibition of 11[beta]-HSD1 completely abolished GIP-induced effects on FFA release. To investigate the acute effects of GIP in humans, a randomized clinical trial was performed. GIP lowered circulating FFAs compared with saline control and reduced expression and ex vivo activity of 11[beta]-HSD1 and adipose triglyceride lipase expression in subcutaneous fat biopsies. Our data suggest that GIP reduces FFA release from adipose tissue by inhibition of lipolysis or by increased reesterification. This process appears to depend on a modification of 11[beta]-HSD1 activity. In general, the presented data support that GIP has direct and insulin-independent effects on adipose tissue. Diabetes 61:292-300, 2012</description><identifier>ISSN: 0012-1797</identifier><identifier>EISSN: 1939-327X</identifier><identifier>DOI: 10.2337/db10-0902</identifier><identifier>CODEN: DIAEAZ</identifier><language>eng</language><publisher>New York: American Diabetes Association</publisher><subject>Adipocytes ; Biopsy ; Body fat ; Dehydrogenases ; Diabetes ; Enzymes ; Fatty acid metabolism ; Fatty acids ; Glucose ; Hormones ; Insulin resistance ; Lipids ; Metabolism ; Physiological aspects ; Polypeptides ; Secretin</subject><ispartof>Diabetes (New York, N.Y.), 2012-02, Vol.61 (2), p.292</ispartof><rights>COPYRIGHT 2012 American Diabetes Association</rights><rights>Copyright American Diabetes Association Feb 2012</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Gogebakan, Ozlem</creatorcontrib><creatorcontrib>Andres, Janin</creatorcontrib><creatorcontrib>Biedasek, Katrin</creatorcontrib><creatorcontrib>Mai, Knut</creatorcontrib><creatorcontrib>Kuhnen, Peter</creatorcontrib><creatorcontrib>Krude, Heiko</creatorcontrib><creatorcontrib>Isken, Frank</creatorcontrib><creatorcontrib>Rudovich, Natalia</creatorcontrib><creatorcontrib>Osterhoff, Martin A</creatorcontrib><creatorcontrib>Kintscher, Ulrich</creatorcontrib><creatorcontrib>Nauck, Michael</creatorcontrib><creatorcontrib>Pfeiffer, Andreas F.H</creatorcontrib><creatorcontrib>Spranger, Joachim</creatorcontrib><title>Glucose-dependent insulinotropic polypeptide reduces fat-specific expression and activity of 11[beta]-hydroxysteroid dehydrogenase type 1 and inhibits release of free fatty acids.(ORIGINAL ARTICLE)</title><title>Diabetes (New York, N.Y.)</title><addtitle>Diabetes</addtitle><description>Glucose-dependent insulinotropic polypeptide (GIP) has been suggested to have direct effects on nonislet tissues. GIP also reportedly increased glucose uptake and inhibition of lipolysis in adipocytes after inhibition of the intracellular cortisone-cortisol shuttle 11[beta]-hydroxysteroid dehydrogenase type 1 (11[beta]-HSD1). We here analyzed whether GIP modifies lipid metabolism and further elucidated the relation between GIP, 11[beta]-HSD1, and fatty acid metabolism. GIP reduced activity of 11[beta]-HSD1 promoter constructs and the expression and activity of 11[beta]-HSD1 in differentiated 3T3-L1 adipocytes in a time- and dose-dependent fashion. This was paralleled by a reduction of free fatty acid (FFA) release and a reduced expression of key enzymes regulating lipolysis in adipose tissue. Preinhibition of 11[beta]-HSD1 completely abolished GIP-induced effects on FFA release. To investigate the acute effects of GIP in humans, a randomized clinical trial was performed. GIP lowered circulating FFAs compared with saline control and reduced expression and ex vivo activity of 11[beta]-HSD1 and adipose triglyceride lipase expression in subcutaneous fat biopsies. Our data suggest that GIP reduces FFA release from adipose tissue by inhibition of lipolysis or by increased reesterification. This process appears to depend on a modification of 11[beta]-HSD1 activity. In general, the presented data support that GIP has direct and insulin-independent effects on adipose tissue. Diabetes 61:292-300, 2012</description><subject>Adipocytes</subject><subject>Biopsy</subject><subject>Body fat</subject><subject>Dehydrogenases</subject><subject>Diabetes</subject><subject>Enzymes</subject><subject>Fatty acid metabolism</subject><subject>Fatty acids</subject><subject>Glucose</subject><subject>Hormones</subject><subject>Insulin resistance</subject><subject>Lipids</subject><subject>Metabolism</subject><subject>Physiological 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fat-specific expression and activity of 11[beta]-hydroxysteroid dehydrogenase type 1 and inhibits release of free fatty acids.(ORIGINAL ARTICLE)</atitle><jtitle>Diabetes (New York, N.Y.)</jtitle><addtitle>Diabetes</addtitle><date>2012-02-01</date><risdate>2012</risdate><volume>61</volume><issue>2</issue><spage>292</spage><pages>292-</pages><issn>0012-1797</issn><eissn>1939-327X</eissn><coden>DIAEAZ</coden><abstract>Glucose-dependent insulinotropic polypeptide (GIP) has been suggested to have direct effects on nonislet tissues. GIP also reportedly increased glucose uptake and inhibition of lipolysis in adipocytes after inhibition of the intracellular cortisone-cortisol shuttle 11[beta]-hydroxysteroid dehydrogenase type 1 (11[beta]-HSD1). We here analyzed whether GIP modifies lipid metabolism and further elucidated the relation between GIP, 11[beta]-HSD1, and fatty acid metabolism. GIP reduced activity of 11[beta]-HSD1 promoter constructs and the expression and activity of 11[beta]-HSD1 in differentiated 3T3-L1 adipocytes in a time- and dose-dependent fashion. This was paralleled by a reduction of free fatty acid (FFA) release and a reduced expression of key enzymes regulating lipolysis in adipose tissue. Preinhibition of 11[beta]-HSD1 completely abolished GIP-induced effects on FFA release. To investigate the acute effects of GIP in humans, a randomized clinical trial was performed. GIP lowered circulating FFAs compared with saline control and reduced expression and ex vivo activity of 11[beta]-HSD1 and adipose triglyceride lipase expression in subcutaneous fat biopsies. Our data suggest that GIP reduces FFA release from adipose tissue by inhibition of lipolysis or by increased reesterification. This process appears to depend on a modification of 11[beta]-HSD1 activity. In general, the presented data support that GIP has direct and insulin-independent effects on adipose tissue. Diabetes 61:292-300, 2012</abstract><cop>New York</cop><pub>American Diabetes Association</pub><doi>10.2337/db10-0902</doi></addata></record> |
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| ispartof | Diabetes (New York, N.Y.), 2012-02, Vol.61 (2), p.292 |
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| language | eng |
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| source | PubMed Central Free; EZB Free E-Journals; Journals@Ovid Complete |
| subjects | Adipocytes Biopsy Body fat Dehydrogenases Diabetes Enzymes Fatty acid metabolism Fatty acids Glucose Hormones Insulin resistance Lipids Metabolism Physiological aspects Polypeptides Secretin |
| title | Glucose-dependent insulinotropic polypeptide reduces fat-specific expression and activity of 11[beta]-hydroxysteroid dehydrogenase type 1 and inhibits release of free fatty acids.(ORIGINAL ARTICLE) |
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