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Adiponectin is essential for lipid homeostasis and survival under insulin deficiency and promotes β-cell regeneration.

Ye R, Holland WL, Gordillo R, Wang M, Wang QA, Shao M, Morley TS, Gupta RK, Stahl A, Scherer PE - Elife (2014)

Bottom Line: When insulin levels are marginal, adiponectin is critical for insulin signaling, endocytosis, and lipid uptake in subcutaneous white adipose tissue.In the absence of both insulin and adiponectin, severe lipoatrophy and hyperlipidemia lead to lethality.In contrast, elevated adiponectin levels improve systemic lipid metabolism in the near absence of insulin.

View Article: PubMed Central - PubMed

Affiliation: Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States.

ABSTRACT
As an adipokine in circulation, adiponectin has been extensively studied for its beneficial metabolic effects. While many important functions have been attributed to adiponectin under high-fat diet conditions, little is known about its essential role under regular chow. Employing a mouse model with inducible, acute β-cell ablation, we uncovered an essential role of adiponectin under insulinopenic conditions to maintain minimal lipid homeostasis. When insulin levels are marginal, adiponectin is critical for insulin signaling, endocytosis, and lipid uptake in subcutaneous white adipose tissue. In the absence of both insulin and adiponectin, severe lipoatrophy and hyperlipidemia lead to lethality. In contrast, elevated adiponectin levels improve systemic lipid metabolism in the near absence of insulin. Moreover, adiponectin is sufficient to mitigate local lipotoxicity in pancreatic islets, and it promotes reconstitution of β-cell mass, eventually reinstating glycemic control. We uncovered an essential new role for adiponectin, with major implications for type 1 diabetes.

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Related in: MedlinePlus

Quantitation of proliferating β-cells.All islets on the pancreas sections were counted and calculated for the percentage of Ki-67+ insulin+ cells (A) or BrdU+ insulin+ cells (B) within the population of insulin+ cells. n ≥ 3 mice per genotype. Data are presented as the mean ± SEM. Related to Figure 7F,G.DOI:http://dx.doi.org/10.7554/eLife.03851.036
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fig7s5: Quantitation of proliferating β-cells.All islets on the pancreas sections were counted and calculated for the percentage of Ki-67+ insulin+ cells (A) or BrdU+ insulin+ cells (B) within the population of insulin+ cells. n ≥ 3 mice per genotype. Data are presented as the mean ± SEM. Related to Figure 7F,G.DOI:http://dx.doi.org/10.7554/eLife.03851.036

Mentions: Enhanced proliferative activity was observed prior to the major regeneration of β-cells in the P-AdnTg/+ mice. Five weeks post ablation, P-AdnTg/+ mice showed higher ratios of Ki-67-positive (Figure 7F and Figure 7—figure supplement 5A) and BrdU-positive (Figure 7G and Figure 7—figure supplement 5B) cells in insulin-positive cells than seen in the islets of P-Adn+/+ or WT mice. The potent adiponectin-driven improvements in systemic lipid metabolism and amelioration of local lipotoxicity may be an important facilitative component towards β-cell proliferation and may contribute to the eventual recovery of islet mass.


Adiponectin is essential for lipid homeostasis and survival under insulin deficiency and promotes β-cell regeneration.

Ye R, Holland WL, Gordillo R, Wang M, Wang QA, Shao M, Morley TS, Gupta RK, Stahl A, Scherer PE - Elife (2014)

Quantitation of proliferating β-cells.All islets on the pancreas sections were counted and calculated for the percentage of Ki-67+ insulin+ cells (A) or BrdU+ insulin+ cells (B) within the population of insulin+ cells. n ≥ 3 mice per genotype. Data are presented as the mean ± SEM. Related to Figure 7F,G.DOI:http://dx.doi.org/10.7554/eLife.03851.036
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4228265&req=5

fig7s5: Quantitation of proliferating β-cells.All islets on the pancreas sections were counted and calculated for the percentage of Ki-67+ insulin+ cells (A) or BrdU+ insulin+ cells (B) within the population of insulin+ cells. n ≥ 3 mice per genotype. Data are presented as the mean ± SEM. Related to Figure 7F,G.DOI:http://dx.doi.org/10.7554/eLife.03851.036
Mentions: Enhanced proliferative activity was observed prior to the major regeneration of β-cells in the P-AdnTg/+ mice. Five weeks post ablation, P-AdnTg/+ mice showed higher ratios of Ki-67-positive (Figure 7F and Figure 7—figure supplement 5A) and BrdU-positive (Figure 7G and Figure 7—figure supplement 5B) cells in insulin-positive cells than seen in the islets of P-Adn+/+ or WT mice. The potent adiponectin-driven improvements in systemic lipid metabolism and amelioration of local lipotoxicity may be an important facilitative component towards β-cell proliferation and may contribute to the eventual recovery of islet mass.

Bottom Line: When insulin levels are marginal, adiponectin is critical for insulin signaling, endocytosis, and lipid uptake in subcutaneous white adipose tissue.In the absence of both insulin and adiponectin, severe lipoatrophy and hyperlipidemia lead to lethality.In contrast, elevated adiponectin levels improve systemic lipid metabolism in the near absence of insulin.

View Article: PubMed Central - PubMed

Affiliation: Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, United States.

ABSTRACT
As an adipokine in circulation, adiponectin has been extensively studied for its beneficial metabolic effects. While many important functions have been attributed to adiponectin under high-fat diet conditions, little is known about its essential role under regular chow. Employing a mouse model with inducible, acute β-cell ablation, we uncovered an essential role of adiponectin under insulinopenic conditions to maintain minimal lipid homeostasis. When insulin levels are marginal, adiponectin is critical for insulin signaling, endocytosis, and lipid uptake in subcutaneous white adipose tissue. In the absence of both insulin and adiponectin, severe lipoatrophy and hyperlipidemia lead to lethality. In contrast, elevated adiponectin levels improve systemic lipid metabolism in the near absence of insulin. Moreover, adiponectin is sufficient to mitigate local lipotoxicity in pancreatic islets, and it promotes reconstitution of β-cell mass, eventually reinstating glycemic control. We uncovered an essential new role for adiponectin, with major implications for type 1 diabetes.

Show MeSH
Related in: MedlinePlus