Combined Insulin Deficiency and Endotoxin Exposure Stimulate Lipid Mobilization and Alter Adipose Tissue Signaling in an Experimental Model of Ketoacidosis in Subjects With Type 1 Diabetes: A Randomized Controlled Crossover Trial

Diabetes
Mads SvartNiels Møller

Abstract

Most often, diabetic ketoacidosis (DKA) in adults results from insufficient insulin administration and acute infection. DKA is assumed to release proinflammatory cytokines and stress hormones that stimulate lipolysis and ketogenesis. We tested whether this perception of DKA can be reproduced in an experimental human model by using combined insulin deficiency and acute inflammation and tested which intracellular mediators of lipolysis are affected in adipose tissue. Nine subjects with type 1 diabetes were studied twice: 1) insulin-controlled euglycemia and 2) insulin deprivation and endotoxin administration (KET). During KET, serum tumor necrosis factor-α, cortisol, glucagon, and growth hormone levels increased, and free fatty acids and 3-hydroxybutyrate concentrations and the rate of lipolysis rose markedly. Serum bicarbonate and pH decreased. Adipose tissue mRNA contents of comparative gene identification-58 (CGI-58) increased and G0/G1 switch 2 gene (G0S2) mRNA decreased robustly. Neither protein levels of adipose triglyceride lipase (ATGL) nor phosphorylations of hormone-sensitive lipase were altered. The clinical picture of incipient DKA in adults can be reproduced by combined insulin deficiency and endotoxin-induced acute ...Continue Reading

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Citations

May 29, 2018·Journal of Diabetes Investigation·Mads SvartHenning Gronbaek
Mar 18, 2020·Pediatric Diabetes·Leonardo Valero-GuzmánTomas Diaz-Angarita
Jun 12, 2020·The Journal of Clinical Endocrinology and Metabolism·Niels Møller
Oct 20, 2020·Endocrine Research·Esben Stistrup LauritzenMette Bjerre
Aug 19, 2021·Physiological Reports·Mads Bisgaard Bengtsen, Niels Møller
Aug 28, 2021·Cardiovascular Drugs and Therapy·Huan ChenYumei Ye

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