glycogen and Bipolar-Disorder

Lithium has the inhibitory effect on many enzymes and multiple effects on some physiological processes. Lithium is also highly effective in the treatment of bipolar disorder, however, the mechanism of lithium action in the treatment of this psychiatric disorder is still unknown. A number of lithium-sensitive enzymes and putative important biomolecules have been proposed as potential targets of lithium action and these mechanisms are discussed in this review.

Topics: Animals; Bipolar Disorder; Brain; Enzyme Inhibitors; Glycogen; Humans; Inositol; Lithium

Topics: Adenylyl Cyclases; Adipose Tissue; Aminobutyrates; Animals; Bipolar Disorder; Blood Glucose; Brain; Brain Chemistry; Cyclic AMP; Diaphragm; Glucose; Glutamates; Glycogen; Humans; Lithium; Liver Glycogen; Muscle, Smooth; Rats

Here we present the data indicating that chronic treatment with three antibipolar drugs, lithium, carbamazepine and valproic acid regulates Cav-1/PTEN/PI3K/AKT/GSK-3β signalling pathway and glycogen content in primary cultured astrocytes. All three drugs down-regulate gene expression of Caveoline 1 (Cav-1), decrease membrane content of phosphatase and tensin homolog (PTEN), increase activity of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and serine-threonine kinase (AKT), and elevate glycogen synthase kinase 3β (GSK-3β) phosphorylation thus suppressing its activity. As expected, treatment with any of these three drugs increases glycogen content in astrocytes. Our findings indicate that regulation of glycogen content via Cav-1/PTEN/AKT/GSK-3β pathway by the three anti-bipoar drugs may be responsible for therapeutic effects of these drugs, and Cav-1 is an important signal element that may contribute to pathogenesis of various CNS diseases and regulation of its gene expression may be one of the underlying mechanisms of drug action for antibipolar drugs and antidepressants currently in clinical use.

Topics: Animals; Animals, Newborn; Antimanic Agents; Astrocytes; Bipolar Disorder; Carbamazepine; Caveolin 1; Cells, Cultured; Dose-Response Relationship, Drug; Glycogen; Glycogen Synthase Kinase 3 beta; Lithium; Mice; Proto-Oncogene Proteins c-akt; PTEN Phosphohydrolase; Signal Transduction; Valproic Acid

Glycogenic hepatopathy (GH) is an underdiagnosed complication of uncontrolled type 1 diabetes mellitus (T1DM). It appears as an acute relapsing hepatitis with reversible transaminase elevations secondary to excessive hepatic glycogen accumulation. Patients are often asymptomatic but can present with abdominal pain, nausea and vomiting. Physical examination shows hepatomegaly without splenomegaly. GH is diagnosed by biopsy as it is clinically indistinguishable from non-alcoholic fatty liver disease (NAFLD), a more common cause of hepatic dysfunction in diabetics. Here we describe a case of GH in a patient with uncontrolled type 1 diabetes whose clinical course was complicated by drug-induced liver injury. The patient initially presented with diabetic ketoacidosis and had a mild transaminitis, thought to be due to NAFLD. She developed profound transaminase elevations while receiving treatment with newer antipsychotic medications for her bipolar disorder. Liver biopsy showed evidence of resolving glycogenic hepatopathy with signs of drug-induced liver injury. This case report reviews the pathology and pathogenesis of GH and reminds the clinician to keep GH within the differential diagnosis for severe transaminitis in a patient with type 1 diabetes mellitus.

Topics: Abdominal Pain; Antipsychotic Agents; Biopsy; Bipolar Disorder; Chemical and Drug Induced Liver Injury; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Diagnosis, Differential; Dibenzocycloheptenes; Female; Glycogen; Hepatomegaly; Heterocyclic Compounds, 4 or More Rings; Humans; Liver; Magnetic Resonance Imaging; Young Adult