Hormone-sensitive lipase, the rate-limiting enzyme in triglyceride hydrolysis, is expressed and active in beta-cells.
Triglycerides in the beta-cell may be important for stimulus-secretion coupling, through provision of a lipid-derived signal, and for pathogenetic events in NIDDM, where lipids may adversely affect beta-cell function. In adipose tissues, hormone-sensitive lipase (HSL) is rate-limiting in triglyceride hydrolysis. Here, we investigated whether this enzyme is also expressed and active in beta-cells. Northern blot analysis and reverse transcription-polymerase chain reaction demonstrated that HSL is expressed in rat islets and in the clonal beta-cell lines INS-1, RINm5F, and HIT-T15. Western blot analysis identified HSL in mouse and rat islets and the clonal beta-cells. In mouse and rat, immunocytochemistry showed a predominant occurrence of HSL in beta-cells, with a presumed cytoplasmic localization. Lipase activity in homogenates of the rodent islets and clonal beta-cells constituted 2.1 +/- 0.6% of that in adipocytes; this activity was immunoinhibited by use of antibodies to HSL. The established HSL expression and activity in beta-cells offer a mechanism whereby lipids are mobilized from intracellular stores. Because HSL in adipocytes is activated by cAMP-dependent protein kinase (PKA), PKA-regulated triglyceride hydrolysis in beta-cells may participate in the regulation of insulin secretion, possibly by providing a lipid-derived signal, e.g., long-chain acyl-CoA and diacylglycerol.
Mulder
H
H
Department of Cell and Molecular Biology, Lund University, Sweden. hindrik.mulder@medkem.lu.se
Holst
L S
LS
Svensson
H
H
Degerman
E
E
Sundler
F
F
Ahrén
B
B
Rorsman
P
P
Holm
C
C
D017667:Adipocytes / Q000201:enzymology; D000818:Animals; D015152:Blotting, Northern; D002999:Clone Cells; D004789:Enzyme Activation / Q000502:physiology; D005455:Fluorescent Antibody Technique; D006868:Hydrolysis; D007515:Islets of Langerhans / Q000166:cytology / Q000201:enzymology*; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D002787:Sterol Esterase / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism*
D014280:Triglycerides; D002787:Sterol Esterase