Udaya Kabadi
University of Iowa, USA
Title: Diabetes Mellitus: Disorder of cellular dysfunction due to lack of entry into cell of glucose; the most efficient fuel for cellular function.
Biography
Biography: Udaya Kabadi
Abstract
Traditionally, diabetes Mellitus has been deemed to be a chronicrnrnhyperglycemic disorder secondary to altered glucose metabolism. Alternatively, hyperglycemia may be one of several manifestations inrnrnsubjects with type 1 and type 2 diabetes Mellitus. Almost all tissuesrnrnrequire insulin for entry of glucose, the possible exceptions being redrnrnblood cells, renal medulla as well as central and peripheral nervousrnrnsystems. Hyperglycemia in intravascular compartment and otherrnrnextra cellular milieu may be attributed to impaired glucose entry intornrnendothelial cells of the vessel wall and almost all other cells includingrnrnhepatocytes, myocytes of all varieties, adipocytes and individual cellsrnrnin most other organs respectively due to absence of insulin in type1rnrnand both the insulin resistance as well as the decline in both phasesrnrnof insulin secretion in type 2 Diabetes. Albeit, the decline in bothrnrnphases of insulin secretion are induced by lack of glucose entry intornrnpancreatic beta cells. Finally, hyperglycemia is perpetuated byrnrnincreased hepatic glucose production caused by into sustainedrnrncirculating hyperglucagonemia secondary to lack of glucose entryrnrninto the pancreatic alpha cells. Alternatively, both the decline inrnrninsulin secretion by the beta cells and the rise in glucagon release byrnrnthe alpha cells are enhanced by fall in GLP1 and GIP caused byrnrndysfunction of L cells and K cells respectively secondary to lack ofrnrnglucose entry in both type 1 and type 2 diabetes. Similarly, increasedrnrnprevalence of infections and thromboembolic micro andrnrnmacrovascular events may be attributed to dysfunction of leukocytesrnrnand platelets respectively due to impaired glucose entry. Finally,rnrnalterations in several other metabolemics including serumrnrnconcentrations of Adiponectin (Adipose cells), TNF alpha,rnrnPlasminogen inhibitor factor 1, Homocysteine, CRP, Lipids etc (rnrnHepatocytes) as well as dysfunction of several organs ( liver, heart,rnrnkidney, adrenal, pituitary, lungs etc) in both type 1 and type 2 diabetesrnrnmay also be attributed to the lack of glucose entry into these specificrnrncells. This hypothesis is validated by improvement in metabolemicsrnrnand organ function on facilitation of glucose entry into cells by insulinrnrnadministration and / or improvement in insulin sensitivity. Therefore,rnrnin conclusion, diabetes mellitus is a disorder manifesting dysfunctionrnrninvolving almost all organs and cells induced by lack of entry ofrnrnglucose, the most efficient substrate for cellular function.