Adiponectin is functionally active in human islets but does not affect insulin secretory function or beta-cell lipoapoptosis.
BACKGROUND
The adipokine adiponectin has insulin-sensitizing, antiatherogenic, and antiinflammatory properties. Mouse and human adiponectin receptor-1 and -2 have been cloned, both of which are expressed in various tissues and mediate effects of globular and full-length adiponectin. Whether adiponectin affects insulin secretion and beta-cell apoptosis and whether plasma adiponectin is associated with beta-cell function in humans is under investigation.


METHODS
In human islets from multiorgan donors, we investigated expression of adiponectin receptor-1 and -2. Furthermore, glucose-stimulated insulin secretion was determined by RIA. In addition, we investigated fatty acid-induced beta-cell apoptosis by terminal dUTP nick end labeling and flow-cytometric cell cycle analysis (sub-G1 formation). In humans in vivo, insulin secretory function was measured during hyperglycemic clamps in 65 normal glucose-tolerant subjects. We determined first and second phase of glucose-stimulated, glucagon-like peptide-1-stimulated, and arginine-stimulated insulin secretion.


RESULTS
Adiponectin receptor-1 and -2 are expressed in human islets at the mRNA and protein level. Moreover, full-length adiponectin induces phosphorylation of acetyl coenzyme A carboxylase. However, adiponectin did not affect basal or glucose-stimulated insulin secretion or basal or fatty acid-induced beta-cell apoptosis. In vivo, fasting plasma adiponectin concentrations were not associated with glucose-stimulated first- and second-phase insulin secretion or with glucagon-like peptide-1- or arginine-stimulated insulin secretion (all P > 0.42).


CONCLUSIONS
These data support a regulatory role of adiponectin in human islets; however, adiponectin does not seem to affect insulin secretion or basal/fatty acid-induced beta-cell apoptosis in humans.
Staiger
K
K
Department of Internal Medicine, University of Tübingen, Otfried-Müller Strasse 10, 72076 Tübingen, Germany.
Stefan
N
N
Staiger
H
H
Brendel
M D
MD
Brandhorst
D
D
Bretzel
R G
RG
Machicao
F
F
Kellerer
M
M
Stumvoll
M
M
Fritsche
A
A
Häring
H-U
HU
D052242:Adiponectin / Q000494:pharmacology / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology
C475418:ADIPOR1 protein, human; C475420:ADIPOR2 protein, human; D052242:Adiponectin; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins