Inter-organ crosstalk during development and progression of type 2 diabetes mellitus

ElSayed, N. A. et al. 2. Classification and diagnosis of diabetes: standards of care in diabetes – 2023. Diabetes Care 46, S19–S40 (2022).

Article  PubMed Central  Google Scholar 

Szendroedi, J. et al. Cohort profile: the German Diabetes Study (GDS). Cardiovasc. Diabetol. 15, 59 (2016).

Article  PubMed  PubMed Central  Google Scholar 

Tabák, A. G. et al. Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study. Lancet 373, 2215–2221 (2009).

Article  PubMed  PubMed Central  Google Scholar 

Roden, M. & Shulman, G. I. The integrative biology of type 2 diabetes. Nature 576, 51–60 (2019). A comprehensive review describing the current understanding of the development of T2DM, specifically addressing the role of lipid mediators.

Article  CAS  PubMed  Google Scholar 

He, X., Kuang, G., Wu, Y. & Ou, C. Emerging roles of exosomal miRNAs in diabetes mellitus. Clin. Transl. Med. 11, e468 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Agbu, P. & Carthew, R. W. MicroRNA-mediated regulation of glucose and lipid metabolism. Nat. Rev. Mol. Cell Biol. 22, 425–438 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mastrototaro, L. & Roden, M. Insulin resistance and insulin sensitizing agents. Metabolism 125, 154892 (2021).

Article  CAS  PubMed  Google Scholar 

Isaac, R., Reis, F. C. G., Ying, W. & Olefsky, J. M. Exosomes as mediators of intercellular crosstalk in metabolism. Cell Metab. 33, 1744–1762 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

James, D. E., Stöckli, J. & Birnbaum, M. J. The aetiology and molecular landscape of insulin resistance. Nat. Rev. Mol. Cell Biol. 22, 751–771 (2021).

Article  CAS  PubMed  Google Scholar 

White, M. F. & Kahn, C. R. Insulin action at a molecular level – 100 years of progress. Mol. Metab. 52, 101304 (2021). A review focusing on the molecular biology of the insulin signalling cascade.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Scherer, P. E. The many secret lives of adipocytes: implications for diabetes. Diabetologia 62, 223–232 (2019).

Article  PubMed  Google Scholar 

Donath, M. Y., Dinarello, C. A. & Mandrup-Poulsen, T. Targeting innate immune mediators in type 1 and type 2 diabetes. Nat. Rev. Immunol. 19, 734–746 (2019).

Article  CAS  PubMed  Google Scholar 

Mirzadeh, Z., Faber, C. L. & Schwartz, M. W. Central nervous system control of glucose homeostasis: a therapeutic target for type 2 diabetes? Annu. Rev. Pharmacol. Toxicol. 62, 55–84 (2022).

Article  PubMed  PubMed Central  Google Scholar 

Rinella, M. E. et al. A multi-society Delphi consensus statement on new fatty liver disease nomenclature. Hepatology https://doi.org/10.1016/j.jhep.2023.06.003 (2023).

Article  PubMed  Google Scholar 

Priest, C. & Tontonoz, P. Inter-organ cross-talk in metabolic syndrome. Nat. Metab. 1, 1177–1188 (2019).

Article  PubMed  Google Scholar 

Herder, C. & Roden, M. A novel diabetes typology: towards precision diabetology from pathogenesis to treatment. Diabetologia 65, 770–1781 (2022).

Article  Google Scholar 

Morze, J. et al. Metabolomics and type 2 diabetes risk: an updated systematic review and meta-analysis of prospective cohort studies. Diabetes Care 45, 1013–1024 (2022). This meta-analysis illustrates the association of numerous lipids and amino acids with increased risk of insulin resistance and T2DM.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Steinhauser, M. L. et al. The circulating metabolome of human starvation. JCI Insight 3, e121434 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Yuan, S., Merino, J. & Larsson, S. C. Causal factors underlying diabetes risk informed by Mendelian randomisation analysis: evidence, opportunities and challenges. Diabetologia 66, 800–812 (2023). This review discusses the findings of Mendelian randomization studies with regard to causality in the development of T2DM.

Article  PubMed  PubMed Central  Google Scholar 

Gancheva, S., Jelenik, T., Álvarez-Hernández, E. & Roden, M. Interorgan metabolic crosstalk in human insulin resistance. Physiol. Rev. 98, 1371–1415 (2018). This review addresses the mechanisms by which metabolites contribute to inter-organ crosstalk in the context of insulin resistance.

Article  CAS  PubMed  Google Scholar 

Gassaway, B. M. et al. PKCε contributes to lipid-induced insulin resistance through cross talk with p70S6K and through previously unknown regulators of insulin signaling. Proc. Natl Acad. Sci. USA 115, e8996–e9005 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Roden, M. et al. Mechanism of free fatty acid-induced insulin resistance in humans. J. Clin. Invest. 97, 2859–2865 (1996).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Stingl, H. et al. Lipid-dependent control of hepatic glycogen stores in healthy humans. Diabetologia 44, 48–54 (2001).

Article  CAS  PubMed  Google Scholar 

Boden, G. & Chen, X. Effects of fat on glucose uptake and utilization in patients with non-insulin-dependent diabetes. J. Clin. Invest. 96, 1261–1268 (1995).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Szendroedi, J. et al. Role of diacylglycerol activation of PKCθ in lipid-induced muscle insulin resistance in humans. Proc. Natl Acad. Sci. USA 111, 9597–9602 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nowotny, B. et al. Mechanisms underlying the onset of oral lipid-induced skeletal muscle insulin resistance in humans. Diabetes 62, 2240–2248 (2013).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sarabhai, T. et al. Dietary palmitate and oleate differently modulate insulin sensitivity in human skeletal muscle. Diabetologia 65, 301–314 (2022). This clinical study shows how differently saturated lipids activate specific cellular pathways to induce insulin resistance in healthy humans.

Article  CAS  PubMed  Google Scholar 

Lyu, K. et al. A membrane-bound diacylglycerol species induces PKCϵ-mediated hepatic insulin resistance. Cell Metab. 32, 654–664.e5 (2020). An interesting study showing the deleterious role of sn-1,2-diacylglycerol in insulin signalling pathways, in humans indirectly by its high levels in the circulation of people with insulin resistance, and in animals directly by showing its mechanism of action.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lyu, K. et al. Short-term overnutrition induces white adipose tissue insulin resistance through sn-1,2-diacylglycerol/PKCε/insulin receptor Thr1160 phosphorylation. JCI Insight 6, e139946 (2021).

PubMed  PubMed Central  Google Scholar 

Jelenik, T. et al. Mechanisms of insulin resistance in primary and secondary nonalcoholic fatty liver. Diabetes 66, 2241–2253 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jelenik, T. et al. Insulin resistance and vulnerability to cardiac ischemia. Diabetes 67, 2695–2702 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Brandon, A. E. et al. Protein kinase C epsilon deletion in adipose tissue, but not in liver, improves glucose tolerance. Cell Metab. 29, 183–191.e7 (2019).

Article  CAS  PubMed  Google Scholar 

Bódis, K. & Roden, M. Energy metabolism of white adipose tissue and insulin resistance in humans. Eur. J. Clin. Invest. 48, e13017 (2018).

Article  PubMed  Google Scholar 

Iqbal, J., Walsh, M. T., Hammad, S. M. & Hussain, M. M. Sphingolipids and lipoproteins in health and metabolic disorders. Trends Endocrinol. Metab. 28, 506–518 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mah, M., Febbraio, M. & Turpin-Nolan, S. Circulating ceramides – are origins important for sphingolipid biomarkers and treatments? Front. Endocrinol. 12, 684448 (2021).

Article  Google Scholar 

Zarini, S. et al. Serum dihydroceramides correlate with insulin sensitivity in humans and decrease insulin sensitivity in vitro. J. Lipid Res. 63, 100270 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Apostolopoulou, M. et al. Specific hepatic sphingolipids relate to insulin resistance, oxidative stress, and inflammation in nonalcoholic steatohepatitis. Diabetes Care 41, 1235–1243 (2018).

Article  CAS  PubMed 

Comments (0)

No login
gif