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Regulation of dipeptidyl peptidase 4 production in adipocytes by glucose.

Das SS, Hayashi H, Sato T, Yamada R, Hiratsuka M, Hirasawa N - Diabetes Metab Syndr Obes (2014)

Bottom Line: However, this difference gradually disappeared over 6 weeks.The stimulation of adipocytes with TNF-α increased the release of DPP4 irrespective of glucose concentration.Our results suggest that the observed increase in serum DPP4 levels may be attributed to increased production of DPP4 in adipocytes and an enhancement in TNF-α-induced release.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan.

ABSTRACT

Objective: Type 1 and 2 diabetes are characterized by elevated blood glucose levels and increased dipeptidyl peptidase 4 (DPP4) activity levels in the serum. However, previous studies reported a negative correlation between glucose concentrations and DPP4 levels. The purpose of this study was to elucidate the connection between glucose and DPP4 in adipocytes under physiological and diabetic conditions, because DPP4 is an adipokine.

Methods: Blood glucose and serum DPP4 levels were measured, and adipocytes were collected from mice under normal, high-fat diet fed, and diabetic conditions. The adipocytes obtained were incubated for 24 hours in medium containing 5.5 or 25 mM glucose, and 3T3-L1 preadipocytes were differentiated under 5.5 or 25 mM glucose. Adipocytes from mice and 3T3-L1 were stimulated by tumor necrosis factor-α (TNF-α) for 24 hours. The levels of released and intracellular DPP4 were determined by enzyme-linked immunosorbent assay.

Results: Mice fed high-fat diet had lower serum DPP4 levels in the first and second week than controls. However, this difference gradually disappeared over 6 weeks. The differentiation of 3T3-L1 adipocytes under 25 mM glucose produced lower DPP4 levels than those differentiated under 5.5 mM; this was also observed in isolated adipocytes from mice. However, these effects of glucose were lost in adipocytes from diabetic mice, and an increase in total DPP4 levels was observed. The stimulation of adipocytes with TNF-α increased the release of DPP4 irrespective of glucose concentration.

Conclusion: The production of DPP4 in adipocytes was negatively regulated by 25 mM glucose under physiological conditions, but not in diabetic mice. Our results suggest that the observed increase in serum DPP4 levels may be attributed to increased production of DPP4 in adipocytes and an enhancement in TNF-α-induced release.

No MeSH data available.


Related in: MedlinePlus

Oil Red O staining of 3T3-L1 adipocytes.Notes: The differentiation of 3T3-L1 preadipocytes to adipocytes was carried out for 10 days 3T3-L1 adipocytes were stained with Oil Red O. (A and B) Representative images of adipocytes grown under the (A) 5.5 mM glucose and (B) 25 mM glucose conditions. (C) Oil Red O contents were determined colormetrically. n=3.Abbreviation: NS, not significant.
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f2-dmso-7-185: Oil Red O staining of 3T3-L1 adipocytes.Notes: The differentiation of 3T3-L1 preadipocytes to adipocytes was carried out for 10 days 3T3-L1 adipocytes were stained with Oil Red O. (A and B) Representative images of adipocytes grown under the (A) 5.5 mM glucose and (B) 25 mM glucose conditions. (C) Oil Red O contents were determined colormetrically. n=3.Abbreviation: NS, not significant.

Mentions: We investigated whether glucose affected differentiation and DPP4 expression in adipocytes. We cultured 3T3-L1 cells under 5.5 (Figure 2A) and 25 mM (Figure 2B) glucose conditions for 10 days and stained with Oil Red O. No significant difference was observed between the lipid levels in adipocytes grown under the 5.5 or 25 mM glucose condition, as quantified by Oil Red O (Figure 2C).


Regulation of dipeptidyl peptidase 4 production in adipocytes by glucose.

Das SS, Hayashi H, Sato T, Yamada R, Hiratsuka M, Hirasawa N - Diabetes Metab Syndr Obes (2014)

Oil Red O staining of 3T3-L1 adipocytes.Notes: The differentiation of 3T3-L1 preadipocytes to adipocytes was carried out for 10 days 3T3-L1 adipocytes were stained with Oil Red O. (A and B) Representative images of adipocytes grown under the (A) 5.5 mM glucose and (B) 25 mM glucose conditions. (C) Oil Red O contents were determined colormetrically. n=3.Abbreviation: NS, not significant.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4043708&req=5

f2-dmso-7-185: Oil Red O staining of 3T3-L1 adipocytes.Notes: The differentiation of 3T3-L1 preadipocytes to adipocytes was carried out for 10 days 3T3-L1 adipocytes were stained with Oil Red O. (A and B) Representative images of adipocytes grown under the (A) 5.5 mM glucose and (B) 25 mM glucose conditions. (C) Oil Red O contents were determined colormetrically. n=3.Abbreviation: NS, not significant.
Mentions: We investigated whether glucose affected differentiation and DPP4 expression in adipocytes. We cultured 3T3-L1 cells under 5.5 (Figure 2A) and 25 mM (Figure 2B) glucose conditions for 10 days and stained with Oil Red O. No significant difference was observed between the lipid levels in adipocytes grown under the 5.5 or 25 mM glucose condition, as quantified by Oil Red O (Figure 2C).

Bottom Line: However, this difference gradually disappeared over 6 weeks.The stimulation of adipocytes with TNF-α increased the release of DPP4 irrespective of glucose concentration.Our results suggest that the observed increase in serum DPP4 levels may be attributed to increased production of DPP4 in adipocytes and an enhancement in TNF-α-induced release.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan.

ABSTRACT

Objective: Type 1 and 2 diabetes are characterized by elevated blood glucose levels and increased dipeptidyl peptidase 4 (DPP4) activity levels in the serum. However, previous studies reported a negative correlation between glucose concentrations and DPP4 levels. The purpose of this study was to elucidate the connection between glucose and DPP4 in adipocytes under physiological and diabetic conditions, because DPP4 is an adipokine.

Methods: Blood glucose and serum DPP4 levels were measured, and adipocytes were collected from mice under normal, high-fat diet fed, and diabetic conditions. The adipocytes obtained were incubated for 24 hours in medium containing 5.5 or 25 mM glucose, and 3T3-L1 preadipocytes were differentiated under 5.5 or 25 mM glucose. Adipocytes from mice and 3T3-L1 were stimulated by tumor necrosis factor-α (TNF-α) for 24 hours. The levels of released and intracellular DPP4 were determined by enzyme-linked immunosorbent assay.

Results: Mice fed high-fat diet had lower serum DPP4 levels in the first and second week than controls. However, this difference gradually disappeared over 6 weeks. The differentiation of 3T3-L1 adipocytes under 25 mM glucose produced lower DPP4 levels than those differentiated under 5.5 mM; this was also observed in isolated adipocytes from mice. However, these effects of glucose were lost in adipocytes from diabetic mice, and an increase in total DPP4 levels was observed. The stimulation of adipocytes with TNF-α increased the release of DPP4 irrespective of glucose concentration.

Conclusion: The production of DPP4 in adipocytes was negatively regulated by 25 mM glucose under physiological conditions, but not in diabetic mice. Our results suggest that the observed increase in serum DPP4 levels may be attributed to increased production of DPP4 in adipocytes and an enhancement in TNF-α-induced release.

No MeSH data available.


Related in: MedlinePlus