Effects of elevated fatty acid and glucose concentrations on pancreatic islet function in vitro.

Abstract

AIMS/HYPOTHESIS:

The aims of this study were to elucidate long-term effects of increased fatty acids and glucose concentrations on islet hormone secretion, triglyceride (TG) accumulation and fuel metabolism, and to determine the role of insulin on glucagon secretion.

METHODS:

Isolated normal mouse islets were exposed to palmitate (0.6 mM) in the presence of high glucose (16.7 mM). After 48 h culture, glucagon secretion and content, insulin secretion and content, TG content and glucose oxidation were measured. The impact of etomoxir, an inhibitor of carnitine palmitoyl transferase-1, as well as of insulin, and alterations in gene expression were also investigated.

RESULTS:

In the presence of palmitate, (i) high glucose caused no statistically significant suppression of glucagon while this was seen in the absence of palmitate; (ii) the insulin response to high glucose was impaired and (iii) an accumulation of TG and a decline in glucose oxidation were detected, whereas the glucagon content remained unchanged. However, etomoxir was capable of reducing glucagon secretion. Addition of exogenous insulin (10(-10)-10(-6) M) failed to restore alpha cell response to normal. Furthermore, 0.6 mM palmitate reduced the mRNA levels of acetyl-CoA carboxylase-1 and sterol regulatory element-binding protein-1c.

CONCLUSIONS/INTERPRETATION:

In summary, high concentrations of palmitate and glucose cause a relative increase in glucagon secretion, a decline in insulin secretion, a loss of alpha cell sensitivity to glucose and an accumulation of TG. The inability of insulin to suppress glucagon may be because of insulin resistance of alpha cells.

• Authors: J Hong, P B Jeppesen, K Hermansen
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 11 Issue 4 Pg. 397-404 (Apr 2009) ISSN: 1463-1326 [Electronic] England
• PMID: 19267716 (Publication Type: Letter, Research Support, Non-U.S. Gov't)

Chemical References

• Insulin
• Palmitic Acid
• Glucagon
• Glucose

Topics

• Animals
• Female
• Glucagon (metabolism)
• Glucose (pharmacology)
• Insulin (metabolism)
• Insulin Secretion
• Islets of Langerhans (drug effects)
• Mice
• Palmitic Acid (pharmacology)
• Tissue Culture Techniques