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Dual actions of apolipoprotein A-I on glucose-stimulated insulin secretion and insulin-independent peripheral tissue glucose uptake lead to increased heart and skeletal muscle glucose disposal

Domingo-Espín, Joan LU ; Lindahl, Maria LU ; Nilsson, Oktawia LU ; Cushman, Samuel W; Stenkula, Karin G. LU and Lagerstedt, Jens O. LU (2016) In Diabetes 65(7). p.1838-1848
Abstract

Apolipoprotein A-I (apoA-I) of HDL is central to the transport of cholesterol in circulation. ApoA-I also provides glucose control with described in vitro effects of apoA-I on β-cell insulin secretion and muscle glucose uptake. In addition, apoA-I injections in insulin-resistant diet-induced obese (DIO) mice lead to increased glucose-stimulated insulin secretion (GSIS) and peripheral tissue glucose uptake. However, the relative contribution of apoA-I as an enhancer of GSIS in vivo and as a direct stimulator of insulin-independent glucose uptake is not known. Here, DIO mice with instant and transient blockade of insulin secretion were used in glucose tolerance tests and in positron emission tomography analyses. Data demonstrate that... (More)

Apolipoprotein A-I (apoA-I) of HDL is central to the transport of cholesterol in circulation. ApoA-I also provides glucose control with described in vitro effects of apoA-I on β-cell insulin secretion and muscle glucose uptake. In addition, apoA-I injections in insulin-resistant diet-induced obese (DIO) mice lead to increased glucose-stimulated insulin secretion (GSIS) and peripheral tissue glucose uptake. However, the relative contribution of apoA-I as an enhancer of GSIS in vivo and as a direct stimulator of insulin-independent glucose uptake is not known. Here, DIO mice with instant and transient blockade of insulin secretion were used in glucose tolerance tests and in positron emission tomography analyses. Data demonstrate that apoA-I to an equal extent enhances GSIS and acts as peripheral tissue activator of insulin-independent glucose uptake and verify skeletal muscle as an apoA-I target tissue. Intriguingly, our analyses also identify the heart as an important target tissue for the apoA-I-stimulated glucose uptake, with potential implications in diabetic cardiomyopathy. Explorations of apoA-I as a novel antidiabetic drug should extend to treatments of diabetic cardiomyopathy and other cardiovascular diseases in patients with diabetes.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
65
issue
7
pages
11 pages
publisher
American Diabetes Association
external identifiers
  • Scopus:84975859218
ISSN
0012-1797
DOI
10.2337/db15-1493
language
English
LU publication?
yes
id
b4320822-d38e-41a0-9be4-9da39f792141
date added to LUP
2016-07-18 16:17:26
date last changed
2016-09-20 03:07:15
@misc{b4320822-d38e-41a0-9be4-9da39f792141,
  abstract     = {<p>Apolipoprotein A-I (apoA-I) of HDL is central to the transport of cholesterol in circulation. ApoA-I also provides glucose control with described in vitro effects of apoA-I on β-cell insulin secretion and muscle glucose uptake. In addition, apoA-I injections in insulin-resistant diet-induced obese (DIO) mice lead to increased glucose-stimulated insulin secretion (GSIS) and peripheral tissue glucose uptake. However, the relative contribution of apoA-I as an enhancer of GSIS in vivo and as a direct stimulator of insulin-independent glucose uptake is not known. Here, DIO mice with instant and transient blockade of insulin secretion were used in glucose tolerance tests and in positron emission tomography analyses. Data demonstrate that apoA-I to an equal extent enhances GSIS and acts as peripheral tissue activator of insulin-independent glucose uptake and verify skeletal muscle as an apoA-I target tissue. Intriguingly, our analyses also identify the heart as an important target tissue for the apoA-I-stimulated glucose uptake, with potential implications in diabetic cardiomyopathy. Explorations of apoA-I as a novel antidiabetic drug should extend to treatments of diabetic cardiomyopathy and other cardiovascular diseases in patients with diabetes.</p>},
  author       = {Domingo-Espín, Joan and Lindahl, Maria and Nilsson, Oktawia and Cushman, Samuel W and Stenkula, Karin G. and Lagerstedt, Jens O.},
  issn         = {0012-1797},
  language     = {eng},
  month        = {07},
  number       = {7},
  pages        = {1838--1848},
  publisher    = {ARRAY(0xaca8bb0)},
  series       = {Diabetes},
  title        = {Dual actions of apolipoprotein A-I on glucose-stimulated insulin secretion and insulin-independent peripheral tissue glucose uptake lead to increased heart and skeletal muscle glucose disposal},
  url          = {http://dx.doi.org/10.2337/db15-1493},
  volume       = {65},
  year         = {2016},
}