Adipose tissue: a key target for diabetes pathophysiology and treatment?
Excess adipose tissue brings with it a number of adverse consequences, many of which may stem from the development of insulin resistance. An emerging view is that inflammatory changes occurring in expanding adipose tissue are associated with the secretion of peptide and other factors that can adversely affect metabolic processes in other key insulin-target tissues, especially liver and skeletal muscle. However, there is still a commonly-expressed view that the adverse changes in other tissues are ultimately due to an excess of fatty acids, liberated by a metabolically-challenged adipose tissue. Our own studies of adipose tissue metabolism and physiological function (especially blood flow) IN VIVO suggest that these two views of adipose tissue function may be closely linked. Enlarged adipocytes are less dynamic in their responses, just as 'enlarged adipose tissue' is less dynamic in blood flow regulation. Adipocytes seem to be able to sense the appropriate level of fat storage. If the normal mechanisms regulating adipocyte fat storage are interfered with (either in genetically-modified animals or by increasing the size of the adipocytes), then perhaps some sort of cellular stress sets in, leading to the inflammatory and endocrine changes. Some evidence for this comes from the effects of the thiazolidinediones, which improve adipose tissue function and in parallel reduce inflammatory changes.
Frayn
K N
KN
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, UK. keith.frayn@oxlip.ox.ac.uk
Tan
G D
GD
Karpe
F
F
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D016503:Drug Delivery Systems; D004703:Endocrine System / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*
D007004:Hypoglycemic Agents