Impairment of substrate-mediated mitochondrial respiration in cardiac cells by chloroquine.

Chloroquine (CQ) has a long clinical history as an anti-malarial agent and also being used for the treatment of other infections and autoimmune diseases. Recently, this lysosomotropic agent and its derivatives are also been tested as adjuncts alongside conventional anti-cancer treatments in combinatorial therapies. However, their reported cardiotoxicity tends to raise concern over their indiscriminate use.

The Effect of Glucagon on Protein Catabolism During Insulin Deficiency: Exchange of Amino Acids Across Skeletal Muscle and the Splanchnic Bed.

Transient insulin deprivation with concurrent hyperglucagonemia is a catabolic state that can occur in type 1 diabetes. To evaluate glucagon's catabolic effect in the setting of its glucogenic effect, we measured the regional exchanges of amino acid metabolites (amino-metabolites) across muscle and splanchnic beds in 16 healthy humans during either somatostatin followed by glucagon or saline infusion alone. Despite a twofold or greater increase in the regional exchange of amino-metabolites by glucagon, whole-body kinetics and concentrations of amino acids (AA) remained stable.

Diminished substrate-mediated cardiac mitochondrial respiration and elevated autophagy in adult male offspring of gestational diabetic rats.

Heart diseases are common in the offspring of diabetic mother (ODM). Defects in mitochondrial metabolism and autophagy may, in part, be responsible for the adverse structural and functional alterations in the heart. The principal objective of this study was to investigate cardiac mitochondrial respiration and autophagy in male and female offspring of diabetic pregnancy at two different developmental stages of life, weaning and adult.

Diminished substrate-mediated cardiac mitochondrial respiration and elevated autophagy in adult male offspring of gestational diabetic rats.

Objective: Heart diseases are common in offspring of gestational diabetic mother (ODM). Defects in mitochondrial metabolism and autophagy may be one of the basic reasons behind the abnormal structural and functional behaviour of offspring's heart. So the main objective of the present study was to explore the cardiac mitochondrial respiration and autophagy in male and female offspring of diabetic pregnancy at two different developmental stages of life.

Impaired substrate-mediated cardiac mitochondrial complex I respiration with unaltered regulation of fatty acid metabolism and oxidative stress status in type 2 diabetic Asian Indians.

Background: The cardiovascular complications associated with type 2 diabetes mellitus could be attributed to changes in myocardial mitochondrial metabolism. Though it is a known fact that permeabilized cardiac muscle fibers and isolated mitochondria are metabolically compromised in the Caucasian population, studies of Asian Indian myocardial mitochondrial function are lacking. Thus, the objective of the present study is to analyze if there is altered cardiac mitochondrial substrate utilization in diabetic Asian Indians.

TFAM Enhances Fat Oxidation and Attenuates High-Fat Diet-Induced Insulin Resistance in Skeletal Muscle.

Diet-induced insulin resistance (IR) adversely affects human health and life span. We show that muscle-specific overexpression of human mitochondrial transcription factor A (TFAM) attenuates high-fat diet (HFD)-induced fat gain and IR in mice in conjunction with increased energy expenditure and reduced oxidative stress. These TFAM effects on muscle are shown to be exerted by molecular changes that are beyond its direct effect on mitochondrial DNA replication and transcription.

Insulin deficiency and intranasal insulin alter brain mitochondrial function: a potential factor for dementia in diabetes.

Despite the strong association between diabetes and dementia, it remains to be fully elucidated how insulin deficiency adversely affects brain functions. We show that insulin deficiency in streptozotocin-induced diabetic mice decreased mitochondrial ATP production and/or citrate synthase and cytochrome oxidase activities in the cerebrum, hypothalamus, and hippocampus. Concomitant decrease in mitochondrial fusion proteins and increased fission proteins in these brain regions likely contributed to altered mitochondrial function.

Functional and proteomic alterations of plasma high density lipoproteins in type 1 diabetes mellitus.

Objective: Higher HDL-cholesterol (HDL-C) is linked to lower cardiovascular risk but individuals with type 1 diabetes mellitus (T1DM) with normal or high HDL-C have higher cardiovascular events compared to age matched non-diabetic controls (ND). We determined whether altered HDL functions despite having normal HDL-C concentration may explain increased cardiovascular risk in T1DM individuals. We also determined whether irreversible posttranslational modifications (PTMs) of HDL bound proteins occur in T1DM individuals with altered HDL functions.

Indian medical students' perspectives on problem-based learning experiences in the undergraduate curriculum: One size does not fit all.

Purpose: Problem-based learning (PBL) is a well-established method for facilitating the learning of basic science concepts in the context of clinical cases. Relevant evidence is lacking regarding PBL's effectiveness and acceptability as perceived by students accustomed to classical traditional teaching in India. Hence, this study gathered students' opinions on PBL versus Traditional teaching methods to generate a foundation for institutional policymaking and ultimately, changes in the policy of regulatory bodies.