作者
Hilal Sekizkardes, Stephanie Therese Chung, Shaji Chacko, Morey W Haymond, Megan Startzell, Mary Walter, Peter J Walter, Marissa Lightbourne, Rebecca J Brown
发表日期
2020/7/1
期刊
The Journal of clinical investigation
卷号
130
期号
7
页码范围
3592-3602
出版商
American Society for Clinical Investigation
简介
BACKGROUND
Postreceptor insulin resistance (IR) is associated with hyperglycemia and hepatic steatosis. However, receptor-level IR (e.g., insulin receptor pathogenic variants, INSR) causes hyperglycemia without steatosis. We examined 4 pathologic conditions of IR in humans to examine pathways controlling lipid metabolism and gluconeogenesis.
METHODS
Cross-sectional study of severe receptor IR (INSR, n = 7) versus postreceptor IR that was severe (lipodystrophy, n = 14), moderate (type 2 diabetes, n = 9), or mild (obesity, n = 8). Lipolysis (glycerol turnover), hepatic glucose production (HGP), gluconeogenesis (deuterium incorporation from body water into glucose), hepatic triglyceride (magnetic resonance spectroscopy), and hepatic fat oxidation (plasma β-hydroxybutyrate) were measured.
RESULTS
Lipolysis was 2- to 3-fold higher in INSR versus …
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H Sekizkardes, ST Chung, S Chacko, MW Haymond… - The Journal of clinical investigation, 2020