Diabetes Mellitus: Disorder of Cellular Dysfunction Due to Lack of Entry into Cell of Glucose. The Most Efficient Fuel for Cellular Function*

Abstract

Background: Diabetes Mellitus is established to be a chronic hyperglycemic disorder secondary to altered glucose metabolism. Alternatively, hyperglycemia may be one of several manifestations in subjects with type 1 and type 2 diabetes Mellitus. Most tissues require insulin for entry of glucose, exceptions being red blood cells, renal medulla and nervous system. Hyperglycemia in intravascular compartment and other extra cellular milieu may be attributed to impaired glucose entry into endothelial cells of the vessel wall and cells in other tissues due to absence of insulin in type 1 and both insulin resistance and decline in insulin secretion in type 2 Diabetes. Objective: Hypothesis is proposed that Diabetes mellitus is a disorder of cellular dysfunction due to lack of entry of glucose, the most efficient fuel. Literature review was conducted to establish the perspective. Results: Declines in both phases of insulin secretion are induced by lack of glucose entry into pancreatic beta cells. Hyperglycemia is perpetuated by increased hepatic glucose production caused by sustained hyperglucagonemia secondary to lack of glucose entry into the pancreatic alpha cells. Moreover, decline in insulin secretion by beta cells and rise in glucagon release by alpha cells are enhanced by fall in GLP1 and GIP caused by dysfunction of L cells and K cells secondary to lack of glucose entry in both types of diabetes. Increased prevalence of infections and thromboembolic events may be attributed to dysfunction of leukocytes and platelets due to impaired glucose entry. Finally, alterations in metabolemics including Adiponectin, TNF alpha, Plasminogen inhibitor factor 1, Homocysteine, CRP, Lipids etc. as well as dysfunction of several organs in both types of diabetes may also be attributed to the lack of glucose entry into specific cells. Hypothesis is validated by improvement in metabolemics and organ function on facilitation of glucose entry into cells by insulin administration and/or improvement in insulin sensitivity. Conclusion: Diabetes mellitus is a disorder manifesting dysfunction involving almost all organs and cells induced by lack of entry of glucose, the most efficient substrate for cellular function.