Single injections of apoA-I acutely improve in vivo glucose tolerance in insulin-resistant mice.
OBJECTIVE
Apolipoprotein A-I (apoA-I), the main protein constituent of HDL, has a central role in the reverse cholesterol-transport pathway, which together with the anti-inflammatory properties of apoA-I/HDL provide cardioprotection. Recent findings of direct stimulation of glucose uptake in muscle by apoA-I/HDL suggest that altered apoA-I and HDL functionality may be a contributing factor to the development of diabetes. We have studied the in vivo effects of short treatments with human apoA-I in a high-fat diet fed mouse model. In addition to native apoA-I, we investigated the effects of the cardioprotective Milano variant (Arg173Cys).


METHODS
Male C57Bl6 mice on a high-fat diet for 2 weeks that received a single injection of human apoA-I proteins (wild-type and Milano) were analysed for blood glucose and insulin levels during a 3 h incubation followed by glucose tolerance tests. Incorporation of injected human apoA-I protein into HDLs was analysed by native gel electrophoresis.


RESULTS
ApoA-I treatment significantly improved insulin secretion and blood glucose clearance in the glucose tolerance test, with an efficiency exceeding that of lean control animals, and led to decreased basal glucose during the 3 h incubation. Notably, the two apoA-I variants triggered insulin secretion and glucose clearance to the same extent.


CONCLUSIONS
ApoA-I treatment leads to insulin- and non-insulin-dependent effects on glucose homeostasis. The experimental model of short-term (2 weeks) feeding of a high-fat diet to C57Bl6 mice provides a suitable and time-efficient system to unravel the resulting tissue-specific mechanisms of acute apoA-I treatment that lead to improved glucose homeostasis.
Department of Experimental Medical Science, Lund University, S-221 84, Lund, Sweden.
Karin G
KG
Stenkula
Maria
M
Lindahl
Jitka
J
Petrlova
Jonathan
J
Dalla-Riva
Olga
O
Göransson
Samuel W
SW
Cushman
Ewa
E
Krupinska
Helena A
HA
Jones
Jens O
JO
Lagerstedt
D000818:Animals; D016632:Apolipoprotein A-I / Q000008:administration & dosage* / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008075:Lipoproteins, HDL; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
D016632:Apolipoprotein A-I; D001786:Blood Glucose; D007328:Insulin; D008075:Lipoproteins, HDL