Glucose-induced de novo synthesis of fatty acyls causes proportional increases in INS-1E cellular lipids

• Raised concentrations of glucose for extended periods of time have detrimental effects on the insulin-producing P-cell. As de novo synthesis of lipids has been observed under such conditions, it was hypothesized that newly formed lipids may preferentially contain saturated fatty acids, which in particular have been associated with impaired beta-cell function. Glucose-induced de novo synthesis of fatty acids in INS-1E cells cultured in 5.5, 11, 20 or 27 mM glucose for 5 days was assessed by high-resolution magic-angle-spinning (HR-MAS) NMR spectroscopy and gas chromatography-mass spectrometry (GC-MS). The glucose origin of the increase in fatty acyls was verified by replacing glucose with [1-C-13]glucose during culture followed by analysis with two-dimensional H-1-C-13 NMR spectroscopy. The composition of the fatty acyls was determined by GC-MS. Fatty acyls determined by HR-MAS H-1 NMR spectroscopy were increased fivefold in INS-1E cells cultured in 20 or 27mM glucose compared with cells cultured in 5.5mM glucose. The five most abundant fatty acids with their relative percentages in INS-1E cells cultured in 5.5 mM glucose were oleate (33%), palmitate (25%), stearate (19%), octadecenoate (13%) and palmitoleate (4.4%). These proportions were not affected by glucose-induced de novo synthesis in INS-1E cells cultured in 11, 20 or 27 mM glucose. It is concluded that glucose-induced de novo lipid synthesis results in accumulation of both saturated and unsaturated fatty acids in specific proportions that are identical with those present under control conditions.

Nyckelord

diabetes

fatty acyls

gas chromatography-mass spectrometry

glucose

high-resolution magic-angle-spinning NMR

INS-1E cells

lipids

metabolomics

MEDICINE

MEDICIN

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