Dataset Information

Pharmacologic or genetic activation of SIRT1 attenuates the fat-induced decrease in beta-cell function in vivo.

ABSTRACT: BACKGROUND:There is evidence that sirtuin 1 (SIRT1), a key regulator of nutrient metabolism, increases ?-cell secretory function. Excess circulating fat, as seen in obesity, has been shown to decrease ?-cell function, an effect that may involve decreased SIRT1 activity. Consequently, SIRT1 activation may increase ?-cell function in conditions of elevated plasma-free fatty acid levels. Here we attempted to attenuate the lipid-induced decrease in ?-cell function in vivo using pharmacological and genetic models of SIRT1 activation. METHODS:Our pharmacologic model involved 48?h intravenous infusion of Wistar rats with either saline or oleate with or without the SIRT1 activator resveratrol. Additionally, we used ?-cell-specific SIRT1 overexpressing (BESTO) mice and wild-type littermates infused for 48?h intravenously with either saline or oleate. In both models, the infusion period was followed by assessment of ?-cell function using the hyperglycemic clamp method. RESULTS:Lipid infusion resulted in a significant decrease in ?-cell function as expected in both rats (p?

SUBMITTER: Desai T

PROVIDER: S-EPMC6424971 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Pharmacologic or genetic activation of SIRT1 attenuates the fat-induced decrease in beta-cell function in vivo.

Desai Tejas T Koulajian Khajag K Ivovic Aleksandar A Breen Danna M DM Luu Lemieux L Tsiani Evangelia L EL Wheeler Michael B MB Giacca Adria A

Nutrition & diabetes 20190319 1

<h4>Background</h4>There is evidence that sirtuin 1 (SIRT1), a key regulator of nutrient metabolism, increases β-cell secretory function. Excess circulating fat, as seen in obesity, has been shown to decrease β-cell function, an effect that may involve decreased SIRT1 activity. Consequently, SIRT1 activation may increase β-cell function in conditions of elevated plasma-free fatty acid levels. Here we attempted to attenuate the lipid-induced decrease in β-cell function in vivo using pharmacologic ...[more]

PMID: 30890694

Similar Datasets

Project description:In mammals, Sirt1, a member of the sirtuin family of proteins, functions as a nicotinamide adenine dinucleotide-dependent protein deactylase, and has important physiological roles, including the regulation of glucose metabolism, cell survival, and mitochondrial respiration. The initial investigations of Sirt1 deficient mice have revealed a phenotype that includes a reduced lifespan, small size, and an increased frequency of abnormal sperm. We have now performed a detailed analysis of the molecular and functional effects of Sirt1 deficiency in the germ line of Sirt1 knock-out (-/-) mice. We find that Sirt1 deficiency markedly attenuates spermatogenesis, but not oogenesis. Numbers of mature sperm and spermatogenic precursors, as early as d15.5 of development, are significantly reduced ( approximately 2-10-fold less; P</=0.004) in numbers in Sirt1-/- mice, whereas Sirt1 deficiency did not effect the efficiency oocyte production following superovulation of female mice. Furthermore, the proportion of mature sperm with elevated DNA damage ( approximately 7.5% of total epididymal sperm; P = 0.02) was significantly increased in adult Sirt1-/- males. Analysis of global gene expression by microarray analysis in Sirt1 deficient testis revealed dysregulated expression of 85 genes, which were enriched (P<0.05) for genes involved in spermatogenesis and protein sumoylation. To assess the function of Sirt1 deficient germ cells, we compared the efficiency of generating embryos and viable offspring in in vitro fertilization (IVF) experiments using gametes from Sirt1-/- and sibling Sirt1+/- mice. While viable animals were derived in both Sirt1-/- X wild type and Sirt1-/- X Sirt1-/- crosses, the efficiency of producing both 2-cell zygotes and viable offspring was diminished when IVF was performed with Sirt1-/- sperm and/or oocytes. Together, these data support an important role for Sirt1 in spermatogenesis, including spermatogenic stem cells, as well as germ cell function.

Dataset Information

Pharmacologic or genetic activation of SIRT1 attenuates the fat-induced decrease in beta-cell function in vivo.

Publications

Pharmacologic or genetic activation of SIRT1 attenuates the fat-induced decrease in beta-cell function in vivo.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets