Insulin Resistance Compensation: Not Just a Matter of β-Cells?
- Bellvitge Biomedical Research Institute, Barcelona, Spain; Endocrine Unit, Hospital Universitari de Bellvitge, Barcelona, Spain; Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, Barcelona, Spain; Department of Clinical Sciences, University of Barcelona L’Hospitalet de Llobregat, Barcelona, Spain
- Corresponding author: Eduard Montanya, .
The global epidemic of type 2 diabetes is largely secondary to insulin resistance induced by obesity and sedentary lifestyles. Most insulin-resistant subjects are able to increase β-cell secretion to meet the increased insulin demand and do not develop diabetes. However, when β-cell compensation fails, type 2 diabetes develops (1,2). Understanding the mechanisms of this compensatory response is of fundamental importance to elucidate the pathophysiology of type 2 diabetes and has implications for the treatment of the disease.
The capacity of β-cell mass to increase in response to insulin resistance is well established in rodents, where it has been able to prevent diabetes even in extreme conditions (3). In humans, β-cell mass expansion has been shown in normal physiological growth (4) and in insulin-resistant conditions such as pregnancy (5) and obesity (6–10). However, β-cell mass increment is more modest in obese humans than in rodents, has not been confirmed in all ethnic backgrounds (11), and shows a large variability among subjects (10,12). Current imaging techniques are not sensitive enough to accurately measure β-cell mass in vivo, and ethical considerations preclude obtaining pancreatic samples from living subjects. Thus, human β-cell mass has been determined in autopsied pancreata. The cross-sectional nature of the studies, the potential interference of pre- and postmortem processes, and the absence of …