Impaired Mitochondrial Function and Insulin Resistance of Skeletal Muscle in Mitochondrial Diabetes

OBJECTIVE - Impaired muscular mitochondrial function is related to common insulin resistance in type 2 diabetes. Mitochondrial diseases frequently lead to diabetes, which is mostly attributed to defective beta-cell mitochondria and secretion. RESEARCH DESIGN AND METHODS - We assessed muscular mitochondrial function and lipid deposition in liver (hepatocellular lipids [HCLs]) and muscle (intramyocellular lipids [IMCLs]) using P-31/H-1 magnetic resonance spectroscopy and insulin sensitivity and endogenous glucose production (EGP) using hyperinsulinemic-euglycemic clamps combined with isotopic tracer dilution in one female patient suffering from MELAS(myopathy,encephalopathy, lactic acidosis, and stroke-like episodes) syndrome and in six control subjects. RESULTS - The MELAS patient showed impaired insulin sensitivity (4.3 vs. 8.6 +/- 0.5 mg . kg(-1) . min(-1)) and suppression of EGP (69 vs. 94 +/- 1%), and her baseline and insulin-stimulated ATP synthesis were reduced (7.3 and 8.9 vs. 10.6 +/- 1.0 and 12.8 +/- 1.3 mu mol . l(-1) . min(-1)) compared with those of the control subjects. HCLs and IMCLs were comparable between the MELAS patient and control subjects. CONCLUSIONS - Impairment of muscle mitochondrial fitness promotes insulin resistance and could thereby contribute to the development of diabetes in some patients with the MELAS syndrome

How Cooper pairs vanish approaching the Mott insulator in Bi2Sr2CaCu2O8+d

The antiferromagnetic ground state of copper oxide Mott insulators is achieved by localizing an electron at each copper atom in real space (r-space). Removing a small fraction of these electrons (hole doping) transforms this system into a superconducting fluid of delocalized Cooper pairs in momentum space (k-space). During this transformation, two distinctive classes of electronic excitations appear. At high energies, the enigmatic 'pseudogap' excitations are found, whereas, at lower energies, Bogoliubov quasi-particles -- the excitations resulting from the breaking of Cooper pairs -- should exist. To explore this transformation, and to identify the two excitation types, we have imaged the electronic structure of Bi2Sr2CaCu2O8+d in r-space and k-space simultaneously. We find that although the low energy excitations are indeed Bogoliubov quasi-particles, they occupy only a restricted region of k-space that shrinks rapidly with diminishing hole density. Concomitantly, spectral weight is transferred to higher energy r-space states that lack the characteristics of excitations from delocalized Cooper pairs. Instead, these states break translational and rotational symmetries locally at the atomic scale in an energy independent fashion. We demonstrate that these unusual r-space excitations are, in fact, the pseudogap states. Thus, as the Mott insulating state is approached by decreasing the hole density, the delocalized Cooper pairs vanish from k-space, to be replaced by locally translational- and rotational-symmetry-breaking pseudogap states in r-space.Comment: This is author's version. See the Nature website for the published versio