Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Diabetologia
Published in: Diabetologia 9/2007

01-09-2007 | Article

Apolipoprotein A-I stimulates AMP-activated protein kinase and improves glucose metabolism

Authors: R. Han, R. Lai, Q. Ding, Z. Wang, X. Luo, Y. Zhang, G. Cui, J. He, W. Liu, Y. Chen

Published in: Diabetologia | Issue 9/2007

Login to get access

Abstract

Aims/hypothesis

In humans, one of the hallmarks of type 2 diabetes is a reduced plasma concentration of HDL and its major protein component, apolipoprotein A-I (APOA-I). However, it is unknown whether APOA-I directly protects against diabetes. The aim of this study was to characterise the functional role of APOA-I in glucose homeostasis.

Methods

The effects of APOA-I on phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-coenzyme A carboxylase (ACC), glucose uptake and endocytosis were analysed in C2C12 myocytes. Glucose metabolism was investigated in Apoa-I knockout (Apoa-I −/−) mice.

Results

APOA-I was able to stimulate the phosphorylation of AMPK and ACC, and elevated glucose uptake in C2C12 myocytes. APOA-I could be endocytosed into C2C12 myotubes through a clathrin-dependent endocytotic process. Inhibition of endocytosis abrogated APOA-I-stimulated AMPK phosphorylation. In Apoa-I −/− mice, AMPK phosphorylation was reduced in skeletal muscle and liver, and expression of gluconeogenic enzymes was increased in liver. In addition, the Apoa-I −/− mice had increased fat content and compromised glucose tolerance.

Conclusions/interpretation

Our data indicate that APOA-I has a protective effect against diabetes via activation of AMPK. ApoA-I deletion in the mouse led to increased fat mass and impaired glucose tolerance.
Literature
1.
Assmann G, Nofer JR (2003) Atheroprotective effects of high-density lipoproteins. Annu Rev Med 54:321–341PubMedCrossRef
2.
Linsel-Nitschke P, Tall AR (2005) HDL as a target in the treatment of atherosclerotic cardiovascular disease. Nat Rev Drug Discov 4:193–205PubMedCrossRef
3.
Oram JF, Heinecke JW (2005) ATP-binding cassette transporter A1: a cell cholesterol exporter that protects against cardiovascular disease. Physiol Rev 85:1343–1372PubMedCrossRef
4.
Silver DL, Tall AR (2001) The cellular biology of scavenger receptor class B type I. Curr Opin Lipidol 12:497–504PubMedCrossRef
5.
Drew BG, Fidge NH, Gallon-Beaumier G, Kemp BE, Kingwell BA (2004) High-density lipoprotein and apolipoprotein AI increase endothelial NO synthase activity by protein association and multisite phosphorylation. Proc Natl Acad Sci USA 101:6999–7004PubMedCrossRef
6.
Reaven GM (1988) Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 37:1595–1607PubMedCrossRef
7.
8.
Dandona P, Aljada A, Chaudhuri A, Mohanty P, Garg R (2005) Metabolic syndrome: a comprehensive perspective based on interactions between obesity, diabetes, and inflammation. Circulation 111:1448–1454PubMedCrossRef
9.
Mooradian AD, Haas MJ, Wong NC (2004) Transcriptional control of apolipoprotein A-I gene expression in diabetes. Diabetes 53:513–520PubMedCrossRef
10.
Frenais R, Ouguerram K, Maugeais C et al (1997) High density lipoprotein apolipoprotein AI kinetics in NIDDM: a stable isotope study. Diabetologia 40:578–583PubMedCrossRef
11.
Murao K, Wada Y, Nakamura T, Taylor AH, Mooradian AD, Wong NC (1998) Effects of glucose and insulin on rat apolipoprotein A-I gene expression. J Biol Chem 273:18959–18965PubMedCrossRef
12.
Morcillo S, Cardona F, Rojo-Martinez G et al (2005) Association between MspI polymorphism of the APO AI gene and type 2 diabetes mellitus. Diabet Med 22:782–788PubMedCrossRef
13.
Klip A, Guma A, Ramlal T, Bilan PJ, Lam L, Leiter LA (1992) Stimulation of hexose transport by metformin in L6 muscle cells in culture. Endocrinology 130:2535–2544PubMedCrossRef
14.
Williamson R, Lee D, Hagaman J, Maeda N (1992) Marked reduction of high density lipoprotein cholesterol in mice genetically modified to lack apolipoprotein A-I. Proc Natl Acad Sci USA 89:7134–7138PubMedCrossRef
15.
16.
Le PU, Benlimame N, Lagana A, Raz A, Nabi IR (2000) Clathrin-mediated endocytosis and recycling of autocrine motility factor receptor to fibronectin fibrils is a limiting factor for NIH-3T3 cell motility. J Cell Sci 113:3227–3240PubMed
17.
Yamauchi T, Kamon J, Minokoshi Y et al (2002) Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 8:1288–1295PubMedCrossRef
18.
Tomas E, Tsao TS, Saha AK et al (2002) Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: acetyl-CoA carboxylase inhibition and AMP-activated protein kinase activation. Proc Natl Acad Sci USA 99:16309–16313PubMedCrossRef
19.
Wu X, Motoshima H, Mahadev K, Stalker TJ, Scalia R, Goldstein BJ (2003) Involvement of AMP-activated protein kinase in glucose uptake stimulated by the globular domain of adiponectin in primary rat adipocytes. Diabetes 52:1355–1363PubMedCrossRef
20.
Larkin JM, Brown MS, Goldstein JL, Anderson RG (1983) Depletion of intracellular potassium arrests coated pit formation and receptor-mediated endocytosis in fibroblasts. Cell 33:273–285PubMedCrossRef
21.
Kahn BB, Alquier T, Carling D, Hardie DG (2005) AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab 1:15–25PubMedCrossRef
22.
Carling D (2004) The AMP-activated protein kinase cascade – a unifying system for energy control. Trends Biochem Sci 29:18–24PubMedCrossRef
23.
24.
Lochhead PA, Salt IP, Walker KS, Hardie DG, Sutherland C (2000) 5-aminoimidazole-4-carboxamide riboside mimics the effects of insulin on the expression of the 2 key gluconeogenic genes PEPCK and glucose-6-phosphatase. Diabetes 49:896–903PubMedCrossRef
25.
Brunham LR, Kruit JK, Pape TD et al (2007) Beta-cell ABCA1 influences insulin secretion, glucose homeostasis and response to thiazolidinedione treatment. Nat Med 13:340–347PubMedCrossRef
26.
de Beer MC, Castellani LW, Cai L, Stromberg AJ, de Beer FC, van der Westhuyzen DR (2004) ApoA-II modulates the association of HDL with class B scavenger receptors SR-BI and CD36. J Lipid Res 45:706–715PubMedCrossRef
27.
Castellani LW, Goto AM, Lusis AJ (2001) Studies with apolipoprotein A-II transgenic mice indicate a role for HDLs in adiposity and insulin resistance. Diabetes 50:643–651PubMedCrossRef
28.
Eckhardt ER, Cai L, Sun B, Webb NR, van der Westhuyzen DR (2004) High density lipoprotein uptake by scavenger receptor SR-BII. J Biol Chem 279:14372–14381PubMedCrossRef
29.
Martinez LO, Jacquet S, Esteve JP et al (2003) Ectopic beta-chain of ATP synthase is an apolipoprotein A-I receptor in hepatic HDL endocytosis. Nature 421:75–79PubMedCrossRef
30.
Kozyraki R, Fyfe J, Kristiansen M et al (1999) The intrinsic factor-vitamin B12 receptor, cubilin, is a high-affinity apolipoprotein A-I receptor facilitating endocytosis of high-density lipoprotein. Nat Med 5:656–661PubMedCrossRef
Metadata
Title
Apolipoprotein A-I stimulates AMP-activated protein kinase and improves glucose metabolism
Authors
R. Han
R. Lai
Q. Ding
Z. Wang
X. Luo
Y. Zhang
G. Cui
J. He
W. Liu
Y. Chen
Publication date
01-09-2007
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 9/2007
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-007-0752-7

Other articles of this Issue 9/2007

Diabetologia 9/2007 Go to the issue

Editorial

Nice insulins, pity about the evidence

Article

Collagen I induction by high glucose levels is mediated by epidermal growth factor receptor and phosphoinositide 3-kinase/Akt signalling in mesangial cells

Article

RETRACTED ARTICLE:l-glutamine supplementation induces insulin resistance in adipose tissue and improves insulin signalling in liver and muscle of rats with diet-induced obesity

Letter

Brain-derived neurotrophic factor (BDNF) and type 2 diabetes. Reply to Lambert GW et al (letter)

Article

Ablation of the gene encoding p66Shc protects mice against AGE-induced glomerulopathy by preventing oxidant-dependent tissue injury and further AGE accumulation

Article

Independent associations of physical activity and cardiorespiratory fitness with metabolic risk factors in children: the European youth heart study
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Image Credits