Insulin secretion and sensitivity in space flight: Diabetogenic effects

• Published in: Nutrition (Burbank, Los Angeles County, Calif.) Los Angeles County, Calif.), 2002-10, Vol.18 (10), p.842-848
• Main Authors: Tobin, Brian W, Uchakin, Peter N, Leeper-Woodford, Sandra K
• Format: Article
• Language: English
• Subjects: amino acids; Amino Acids - metabolism; Animals; diabetes; Diabetes Mellitus - etiology; disposition index; glucose; Glucose - metabolism; glucose tolerance; Humans; insulin; Insulin - metabolism; Insulin Resistance; Insulin Secretion; Islets of Langerhans - cytology; Islets of Langerhans - metabolism; Life Sciences (General); microgravity; muscle; Muscle Proteins - metabolism; nutrition; protein; Space Flight; Space life sciences; Tumor Necrosis Factor-alpha - metabolism; Tumor Necrosis Factor-alpha - physiology; Weightlessness - adverse effects
• ISSN: 0899-9007; 1873-1244
• DOI: 10.1016/S0899-9007(02)00940-1

Nearly three decades of space flight research have suggested that there are subclinical diabetogenic changes that occur in microgravity. Alterations in insulin secretion, insulin sensitivity, glucose tolerance, and metabolism of protein and amino acids support the hypothesis that insulin plays an essential role in the maintenance of muscle mass in extended-duration space flight. Experiments in flight and after flight and ground-based bedrest studies have associated microgravity and its experimental paradigms with manifestations similar to those of diabetes, physical inactivity, and aging. We propose that these manifestations are characterized best by an etiology that falls into the clinical category of “other” causes of diabetes, including, but not restricted to, genetic β-cell defects, insulin action defects, diseases of the endocrine pancreas, endocrinopathies, drug or chemically induced diabetes, infections, immune-mediated metabolic alteration, and a host of genetic related diseases. We present data showing alterations in tumor necrosis factor-α production, insulin secretion, and amino acid metabolism in pancreatic islets of Langerhans cultured in a ground-based cell culture bioreactor that mimics some of the effects of microgravity. Taken together, space flight research, ground-based studies, and bioreactor studies of pancreatic islets of Langerhans support the hypothesis that the pancreas is unable to overcome peripheral insulin resistance and amino acid dysregulation during space flight. We propose that measures of insulin secretion and insulin action will be necessary to design effective countermeasures against muscle loss, and we advance the “disposition index” as an essential model to be used in the clinical management of space flight–induced muscle loss.