Figure 1.
Characterization of adiponectin batches used for in vivo studies.
A. Analytical size-exclusion chromatography of the batches. The grey bars at the top indicate the approximate elution positions of the various oligomeric forms of adiponectin. B and C. Coomassie stained SDS-PAGE analysis of the batches comparing reduced and non-reduced samples using a Bis-Tris (B) and a Tris-acetate (C) buffer system, respectively. Due to shortage of original sample mgAd was only analyzed reduced and on the Bis-Tris gel.
Table 1.
Overview of the various forms of Adiponectin used in the described in vivo studies.
Figure 2.
Stimulation of ACC phosphorylation in hepatocytes.
Purified trimeric hAd (open squares), hexameric hAd (closed triangles), HMW hAd (open triangles) and 1 mM AICAR (closed circle, located at 3 µM) was used to stimulate ACC phosphorylation (pACC) in primary rat hepatocytes.
Figure 3.
Inhibition of palmitate-induced MCP-1 production by THP-1 cells.
hAd consistently and dose dependently inhibits the MCP-1 release. THP-1 cells were pre-incubated with 10 pM to 1 µM hAd for 2 h and subsequently stimulated with 100 µM palmitate for 24 h. Two different batches of hAd were compared (upward- and downward-pointing triangles) with controls with (square) and without (circle) palmitate.
Figure 4.
Pharmacokinetics of hAd in Sprague Dawley rats.
At t = 0 hAd was dosed i.v. at 4.1 mg/kg (open circles), i.p. at 4.1 mg/kg (open triangles) or i.p. at 13.4 mg/kg (closed triangles). n = 2–5.
Figure 5.
In vivo effects of hAd on glycaemic control in diabetic db/db mice.
The animals were dosed intraperitoneally once daily with metformin (closed triangles) or twice daily with hAd (open squares) or vehicle (open circles) for 14 days. Blood glucose profiles were taken at day 0 (A), day 6 (B) and day 13 (C) of the study at 7 a.m., 10 a.m., 1 p.m., 3 p.m., 6 p.m., and 9 p.m. HbA1c (D) was measured on the same days and additionally 7 and 14 days before the start of dosing. Body weight (E) was monitored daily. The data is representative for all studies performed with db/db mice. The data for all other forms of adiponectin is summarized in Table 2.
Table 2.
Data from db/db mice studies (mean ± SEM).
Table 3.
Data from diabetic Psammomys obesus study (mean ± SEM).