Abstract
Background:Type 2 diabetes stems from obesity-associated insulin resistance, and in the genetically susceptible, concomitant pancreatic β-cell failure can occur, which further exacerbates hyperglycemia. Recent work by our group and others has shown that the natural polyphenol curcumin attenuates the development of insulin resistance and hyperglycemia in mouse models of hyperinsulinemic or compensated type 2 diabetes. Although several potential downstream molecular targets of curcumin exist, it is now recognized to be a direct inhibitor of proteasome activity. We now show that curcumin also prevents β-cell failure in a mouse model of uncompensated obesity-related insulin resistance (Leprdb/db on the Kaliss background).Results:In this instance, dietary supplementation with curcumin prevented hyperglycemia, increased insulin production and lean body mass, and prolonged lifespan. In addition, we show that short-term in vivo treatment with low dosages of two molecularly distinct proteasome inhibitors celastrol and epoxomicin reverse hyperglycemia in mice with β-cell failure by increasing insulin production and insulin sensitivity.Conclusions:These studies suggest that proteasome inhibitors may prove useful for patients with diabetes by improving both β-cell function and relieving insulin resistance.
Highlights
Diabetes is a disease in which the body does not sufficiently produce and/or respond to insulin, a pancreatic endocrine hormone crucial for maintaining glucose homeostasis
In this series of studies, we demonstrate that curcumin treatment enhances β-cell function and proliferation both in vitro and in vivo, and we implicate its inhibitory actions on blood glucose levels using a Freestyle Flash glucometer (Abbott, Abbott Park, IL, USA) and 25 μl was used to assess hemoglobin A1c (HbA1c) using a Bayer DCA 2000+ analyzer (Siemens, Tarrytown, NY, USA)
4% fat 35% fat 4% fat RESULTS Effects of curcumin on glucose homeostasis in obese diabetic mice To investigate the effects of curcumin in a mouse model of severe
Summary
Diabetes is a disease in which the body does not sufficiently produce and/or respond to insulin, a pancreatic endocrine hormone crucial for maintaining glucose homeostasis. Type 2 diabetes stems from obesity-associated insulin resistance, and in the genetically susceptible, concomitant pancreatic β-cell failure can occur, which further exacerbates hyperglycemia. Recent work by our group and others has shown that the natural polyphenol curcumin attenuates the development of insulin resistance and hyperglycemia in mouse models of hyperinsulinemic or compensated type 2 diabetes. We show that curcumin prevents β-cell failure in a mouse model of uncompensated obesity-related insulin resistance (Leprdb/db on the Kaliss background). RESULTS: In this instance, dietary supplementation with curcumin prevented hyperglycemia, increased insulin production and lean body mass, and prolonged lifespan. We show that short-term in vivo treatment with low dosages of two molecularly distinct proteasome inhibitors celastrol and epoxomicin reverse hyperglycemia in mice with β-cell failure by increasing insulin production and insulin sensitivity. CONCLUSIONS: These studies suggest that proteasome inhibitors may prove useful for patients with diabetes by improving both β-cell function and relieving insulin resistance
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