Fatty acids and insulin modulate myocardial substrate metabolism in humans with type 1 diabetes

Linda R. Peterson, Pilar Herrero, Janet McGill, Kenneth B. Schechtman, Zulfia Kisrieva-Ware, Donna Lesniak, Robert J. Gropler

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

OBJECTIVE - Normal human myocardium switches substrate metabolism preference, adapting to the prevailing plasma substrate levels and hormonal milieu, but in type 1 diabetes, the myocardium relies heavily on fatty acid metabolism for energy. Whether conditions that affect myocardial glucose use and fatty acid utilization, oxidation, and storage in nondiabetic subjects alter them in type 1 diabetes is not well known. RESEARCH DESIGN AND METHODS - To test the hypotheses that in humans with type 1 diabetes, myocardial glucose and fatty acid metabolism can be manipulated by altering plasma free fatty acid (FFA) and insulin levels, we quantified myocardial oxygen consumption (MVO 2), glucose, and fatty acid metabolism in nondiabetic subjects and three groups of type 1 diabetic subjects (those studied during euglycemia, hyperlipidemia, and a hyperinsulinemic-euglycemic clamp) using positron emission tomography. RESULTS - Type 1 diabetic subjects had higher MVO2 and lower myocardial glucose utilization rate/insulin than control subjects. In type 1 diabetes, glucose utilization increased with increasing plasma insulin and decreasing FFA levels. Myocardial fatty acid utilization, oxidation, and esterification rates increased with increasing plasma FFA. Increasing plasma insulin levels decreased myocardial fatty acid esterification rates but increased the percentage of fatty acids going into esterification. CONCLUSIONS - Type 1 diabetes myocardium has increased MVO2 and is insulin resistant during euglycemia. However, its myocardial glucose and fatty acid metabolism still responds to changes in plasma insulin and plasma FFA levels. Moreover, insulin and plasma FFA levels can regulate the intramyocardial fate of fatty acids in humans with type 1 diabetes.

Original languageEnglish
Pages (from-to)32-40
Number of pages9
JournalDiabetes
Volume57
Issue number1
DOIs
StatePublished - Jan 2008

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