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Cited by 267

The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

Caloric restriction reverses hepatic insulin resistance in aging rats by decreasing visceral fat.

Open access
Barzilai, N, Banerjee, S, Hawkins, M, Chen, W, Rossetti, L·1998·Journal of Clinical Investigation
DOI 10.1172/jci485
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Abstract

Hyperinsulinemia and increased visceral/abdominal fat (VF) are common features of human aging. To examine the relationships among VF, peripheral, and hepatic insulin sensitivity, we studied 4- and 18-mo-old male Sprague-Dawley rats (n = 42) fed ad libitum (4 AL and 18 AL) or moderately calorie restricted (18 CR) up to 18 mo of age. Total fat mass (FM) and VF were decreased in 18 CR to approximately one-third of that of 18 AL (P < 0.001), while lean body mass (LBM) was unchanged. Most important, 18 CR had more FM (65+/-6 vs. 45+/-6 g) but less VF (7.8+/-0.6 vs. 12.3+/-3.3 g) compared with 4 AL (P < 0.01 for both). Thus, the effects of variable VF on HIS could be assessed, independent of FM and age. Marked hepatic insulin resistance ensued with aging (18 AL) and CR restored hepatic insulin sensitivity to the levels of young rats, while peripheral insulin sensitivity remained unchanged (by insulin clamp of 18 mU/kg/min). In fact, the rates of insulin infusion required to maintain basal hepatic glucose production in the presence of pancreatic clamp were 0.75+/-0.10, 1.41+/-0.13, and 0.51+/-0.12 mU/kg . min, in 4 AL, 18 AL, and 18 CR, respectively (P < 0.01 between all groups), and in 18 CR rats infused with insulin at similar rates as in the 18 AL (1.4 mU/kg/min) hepatic glucose production was decreased by 32% (P < 0. 005). Furthermore, when 18 CR rats were fed AL for 14 d, VF rapidly and selectively increased and severe hepatic insulin resistance was induced. We propose that in this animal model the age-associated decrease in hepatic (rather than peripheral) insulin action is the major determinant of fasting hyperinsulinemia and that increased visceral adiposity plays the major role in inducing hepatic insulin resistance. Thus, interventions designed to prevent the accumulation of VF are likely to represent an effective mean to improve carbohydrate metabolism in aging.

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Metadata

Authors
Barzilai, N., Banerjee, S., Hawkins, M., Chen, W., & Rossetti, L.
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
1998-04-01
Volume
101
Issue
7
Pages
1353-1361
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci485
OpenAlex
W2001854860
Cited by
267
References
6
FWCI
4.76
Type
journal article
Language
en
Open access
green

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