0485 : Subsarcolemmal and interfibrillar mitochondria in human atrial cardiomyocyte: an enzymatic and proteomic study in diabetic patients

Diabetic cardiomyopathy is the leading cause of heart failure among diabetic patients, and mitochondrial dysfunction has been implicated as an underlying cause in the pathogenesis. Cardiac mitochondria consist of two spatially, functionally, and morphologically distinct subpopulations, termed subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM). SSM are situated beneath the plasma membrane, whereas IFM are embedded between myofibrils. The goal of this study was to determine whether spatially distinct cardiac mitochondrial subpopulations respond differently to a diabetic phenotype. Swiss-Webster mice were subjected to intraperitoneal injections of streptozotocin or citrate saline vehicle. Five weeks after injections, diabetic hearts displayed decreased rates of contraction, relaxation, and left ventricular developed pressures ( P < 0.05 for all three). Both mitochondrial size (forward scatter, P < 0.01) and complexity (side scatter, P < 0.01) were decreased in diabetic IFM but not diabetic SSM. Electron transport chain complex II respiration was decreased in diabetic SSM ( P < 0.05) and diabetic IFM ( P < 0.01), with the decrease being greater in IFM. Furthermore, IFM complex I respiration and complex III activity were decreased with diabetes ( P < 0.01) but were unchanged in SSM. Superoxide production was increased only in diabetic IFM ( P < 0.01). Oxidative damage to proteins and lipids, indexed through nitrotyrosine residues and lipid peroxidation, were higher in diabetic IFM ( P < 0.05 and P < 0.01, respectively). The mitochondria-specific phospholipid cardiolipin was decreased in diabetic IFM ( P < 0.01) but not SSM. These results indicate that diabetes mellitus imposes a greater stress on the IFM subpopulation, which is associated, in part, with increased superoxide generation and oxidative damage, resulting in morphological and functional abnormalities that may contribute to the pathogenesis of diabetic cardiomyopathy.

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Intramuscular Nerve and Neuromuscular Junction Alteration In Extraocular Muscles of Diabetic Mice

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100120102 ◽

1985 ◽

Vol 43 ◽

pp. 682-683

Author(s):

Bruce R. Pachter

Keyword(s):

Diabetes Mellitus ◽

Peripheral Nerves ◽

Sudden Onset ◽

Extraocular Muscles ◽

Diabetic Patients ◽

Oculomotor Palsy ◽

Third Nerve Palsy ◽

Patients With Diabetes ◽

Intramuscular Nerve ◽

Oculomotor Nerves

Diabetes mellitus is one of the commonest causes of neuropathy. Diabetic neuropathy is a heterogeneous group of neuropathic disorders to which patients with diabetes mellitus are susceptible; more than one kind of neuropathy can frequently occur in the same individual. Abnormalities are also known to occur in nearly every anatomic subdivision of the eye in diabetic patients. Oculomotor palsy appears to be common in diabetes mellitus for their occurrence in isolation to suggest diabetes. Nerves to the external ocular muscles are most commonly affected, particularly the oculomotor or third cranial nerve. The third nerve palsy of diabetes is characteristic, being of sudden onset, accompanied by orbital and retro-orbital pain, often associated with complete involvement of the external ocular muscles innervated by the nerve. While the human and experimental animal literature is replete with studies on the peripheral nerves in diabetes mellitus, there is but a paucity of reported studies dealing with the oculomotor nerves and their associated extraocular muscles (EOMs).

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A Comparison Between Sterological Point Counting and Digitizing Tablets

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100120023 ◽

1985 ◽

Vol 43 ◽

pp. 666-667

Author(s):

John M. Basgen ◽

Eileen N. Ellis ◽

S. Michael Mauer ◽

Michael W. Steffes

Keyword(s):

Electron Microscopy ◽

Kidney Tissue ◽

Volume Density ◽

Diabetic Patients ◽

Normal Kidney ◽

Point Counting ◽

Normal Kidney Tissue ◽

Biopsy Specimens ◽

Mitochondrial Volume ◽

Kidney Lesions

To determine the efficiency of methods of quantitation of the volume density of components within kidney biopsies, techniques involving a semi-automatic digitizing tablet and stereological point counting were compared.Volume density (Vv) is a parameter reflecting the volume of a component to the volume that contains the component, e.g., the fraction of cell volume that is made up of mitochondrial volume. The units of Vv are μm3 /μm3.Kidney biopsies from 15 patients were used. Five were donor biopsies performed at the time of kidney transplantation (patients 1-5, TABLE 1) and were considered normal kidney tissue. The remaining biopsies were obtained from diabetic patients with a spectrum of diabetic kidney lesions. The biopsy specimens were fixed and embedded according to routine electron microscogy protocols. Three glomeruli from each patient were selected randomly for electron microscopy. An average of 12 unbiased and systematic micrographs were obtained from each glomerulus and printed at a final magnification of x18,000.

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