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Morphine induces physiological, structural, and molecular benefits in the diabetic myocardium
Author(s) -
ZemljicHarpf Alice E.,
See Hoe Louise E.,
Schilling Jan M.,
ZunigaHertz Juan P.,
Nguyen Alexander,
Vaishnav Yash J.,
Belza Gianna J.,
Budiono Boris P.,
Patel Piyush M.,
Head Brian P.,
Dillmann Wolfgang H.,
Mahata Sushil K.,
Peart Jason N.,
Roth David M.,
Headrick John P.,
Patel Hemal H.
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201903233r
Subject(s) - medicine , cardiac function curve , cardioprotection , endocrinology , mitochondrion , mitochondrial permeability transition pore , glucose homeostasis , diabetes mellitus , ischemia , heart failure , morphine , cardiology , insulin resistance , biology , programmed cell death , microbiology and biotechnology , apoptosis , biochemistry
The obesity epidemic has increased type II diabetes mellitus (T2DM) across developed countries. Cardiac T2DM risks include ischemic heart disease, heart failure with preserved ejection fraction, intolerance to ischemia‐reperfusion (I‐R) injury, and refractoriness to cardioprotection. While opioids are cardioprotective, T2DM causes opioid receptor signaling dysfunction. We tested the hypothesis that sustained opioid receptor stimulus may overcome diabetes mellitus‐induced cardiac dysfunction via membrane/mitochondrial‐dependent protection. In a murine T2DM model, we investigated effects of morphine on cardiac function, I‐R tolerance, ultrastructure, subcellular cholesterol expression, mitochondrial protein abundance, and mitochondrial function. T2DM induced 25% weight gain, hyperglycemia, glucose intolerance, cardiac hypertrophy, moderate cardiac depression, exaggerated postischemic myocardial dysfunction, abnormalities in mitochondrial respiration, ultrastructure and Ca 2+ ‐induced swelling, and cell death were all evident. Morphine administration for 5 days: (1) improved glucose homeostasis; (2) reversed cardiac depression; (3) enhanced I‐R tolerance; (4) restored mitochondrial ultrastructure; (5) improved mitochondrial function; (6) upregulated Stat3 protein; and (7) preserved membrane cholesterol homeostasis. These data show that morphine treatment restores contractile function, ischemic tolerance, mitochondrial structure and function, and membrane dynamics in type II diabetic hearts. These findings suggest potential translational value for short‐term, but high‐dose morphine administration in diabetic patients undergoing or recovering from acute ischemic cardiovascular events.