Effects of olanzapine on glucose transport, proliferation and survival in C2C12 myoblasts

Giovanni Tulipano1, PierFranco Spano, Daniela Cocchi

  • 1Division of Pharmacology and Toxicology, Department of Biomedical Sciences and Biotechnologies, University of Brescia, Brescia, Italy. tulipano@med.unibs.it

Insights

Atypical antipsychotics like olanzapine directly impact muscle cell glucose uptake, potentially influencing diabetes risk. Clozapine showed no effect on glucose transport in this study.

Area of Science:

  • Pharmacology
  • Cell Biology
  • Metabolism

Background:

  • Atypical antipsychotics are associated with increased diabetes risk.
  • The direct cellular mechanisms underlying this risk are not fully understood.

Purpose of the Study:

  • To investigate the direct effects of atypical antipsychotics on skeletal muscle cell functions.
  • To determine the potential diabetic liability of these drugs at the cellular level.

Main Methods:

  • In vitro study using mouse skeletal muscle satellite cells (C2C12).
  • Assessed basal and insulin-stimulated glucose uptake (2-deoxyglucose uptake).
  • Evaluated effects on cell proliferation, survival, differentiation, and myotube growth.

Main Results:

  • Olanzapine and alpha-methyl-5-HT dose-dependently stimulated glucose uptake in C2C12 myoblasts.
  • Clozapine did not affect glucose transport.
  • Olanzapine increased plasma membrane GLUT4 abundance, suggesting enhanced glucose transport.
  • Neither clozapine nor olanzapine affected myoblast/myotube proliferation, survival, or growth.

Conclusions:

  • Olanzapine enhances glucose uptake in muscle cells, potentially through GLUT4 translocation.
  • These findings provide cellular insights into the metabolic side effects of atypical antipsychotics.
  • The observed in vitro effects align with in vivo observations of glucose changes prior to weight gain.

Related Concept Videos

Oral Hypoglycemic Agents: Biguanides and Glitazones01:26

Oral Hypoglycemic Agents: Biguanides and Glitazones

Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood glucose levels...
Antiepileptic Drugs: Potassium Channel Activators01:20

Antiepileptic Drugs: Potassium Channel Activators

Ezocgabine or retigabine, an antiepileptic drug of remarkable efficacy, has revolutionized the management of seizures. It is a potassium channel activator, explicitly targeting the family of Q subtype potassium channels. It enhances the transmembrane potassium currents, regulating neuronal excitability. This action stabilizes the resting membrane potential, a pivotal factor in mitigating the hyperexcitability that characterizes epilepsy.
Ezogabine has gained approval as an adjunctive treatment...
Glucose Absorption Into the Small Intestine01:26

Glucose Absorption Into the Small Intestine

Complex carbohydrates consumed cannot be absorbed into the small intestine in their original form. First, they must be hydrolyzed to a monosaccharide form such as glucose or galactose. These monosaccharides are then transported across the intestinal membrane and into the blood via transcellular transport. The intestinal epithelial cells allow the movement of these monosaccharides with a defined 'entry' through membrane transporter proteins present on their apical membrane and 'exit' via the...
Glucose Transporters01:27

Glucose Transporters

Glucose transporters facilitate the transport of glucose across the cell membrane. In addition to glucose, some glucose transporters can also aid the movement of other hexoses such as fructose, mannose, and galactose.
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes: