Universität zu Köln

Franko, Andras ORCID: 0000-0003-0485-5439, Kunze, Alexander, Boese, Marlen, von Kleist-Retzow, Juergen-Christoph, Paulsson, Mats, Hartmann, Ursula and Wiesner, Rudolf J. (2017). Impaired Insulin Signaling is Associated with Hepatic Mitochondrial Dysfunction in IR+/--IRS-1(+/-) Double Heterozygous (IR-IRS1dh) Mice. Int. J. Mol. Sci., 18 (6). BASEL: MDPI AG. ISSN 1422-0067

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Abstract

Mitochondria play a pivotal role in energy metabolism, but whether insulin signaling per se could regulate mitochondrial function has not been identified yet. To investigate whether mitochondrial function is regulated by insulin signaling, we analyzed muscle and liver of insulin receptor (IR)(+/-)-insulin receptor substrate-1 (IRS-1)(+/-) double heterozygous (IR-IRS1dh) mice, a well described model for insulin resistance. IR-IRS1dh mice were studied at the age of 6 and 12 months and glucose metabolism was determined by glucose and insulin tolerance tests. Mitochondrial enzyme activities, oxygen consumption, and membrane potential were assessed using spectrophotometric, respirometric, and proton motive force analysis, respectively. IR-IRS1dh mice showed elevated serum insulin levels. Hepatic mitochondrial oxygen consumption was reduced in IR-IRS1dh animals at 12 months of age. Furthermore, 6-month-old IR-IRS1dh mice demonstrated enhanced mitochondrial respiration in skeletal muscle, but a tendency of impaired glucose tolerance. On the other hand, 12-month-old IR-IRS1dh mice showed improved glucose tolerance, but normal muscle mitochondrial function. Our data revealed that deficiency in IR/IRS-1 resulted in normal or even elevated skeletal muscle, but impaired hepatic mitochondrial function, suggesting a direct cross-talk between insulin signaling and mitochondria in the liver.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Franko, Andras UNSPECIFIED orcid.org/0000-0003-0485-5439 UNSPECIFIED Kunze, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Boese, Marlen UNSPECIFIED UNSPECIFIED UNSPECIFIED von Kleist-Retzow, Juergen-Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Paulsson, Mats UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartmann, Ursula UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiesner, Rudolf J. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-228576
DOI:	10.3390/ijms18061156
Journal or Publication Title:	Int. J. Mol. Sci.
Volume:	18
Number:	6
Date:	2017
Publisher:	MDPI AG
Place of Publication:	BASEL
ISSN:	1422-0067
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DIABETES-MELLITUS; SKELETAL-MUSCLE; ADIPOSE-TISSUE; RESISTANCE; OBESITY; SENSITIVITY; METABOLISM; RECEPTOR; LIVER; AVAILABILITY Multiple languages Biochemistry & Molecular Biology; Chemistry, Multidisciplinary Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22857