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Glycemic control promotes pancreatic beta-cell regeneration in streptozotocin-induced diabetic mice.

Grossman EJ, Lee DD, Tao J, Wilson RA, Park SY, Bell GI, Chong AS - PLoS ONE (2010)

Bottom Line: Defining the conditions that promote beta-cell proliferation could benefit patients with diabetes.The results show that insulin treatment can promote beta-cell regeneration.Moreover, the extent of restoration of beta-cell function and mass depend on the length of treatment period and overall level of glycemic control with better control being associated with improved recovery.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, The University of Chicago, Chicago, Illinois, United States of America. eric.grossman@uchospitals.edu

ABSTRACT

Background: Pancreatic beta-cells proliferate following administration of the beta-cell toxin streptozotocin. Defining the conditions that promote beta-cell proliferation could benefit patients with diabetes. We have investigated the effect of insulin treatment on pancreatic beta-cell regeneration in streptozotocin-induced diabetic mice, and, in addition, report on a new approach to quantify beta-cell regeneration in vivo.

Methodology/principal findings: Streptozotocin-induced diabetic were treated with either syngeneic islets transplanted under the kidney capsule or subcutaneous insulin implants. After either 60 or 120 days of insulin treatment, the islet transplant or insulin implant were removed and blood glucose levels monitored for 30 days. The results showed that both islet transplants and insulin implants restored normoglycemia in the 60 and 120 day treated animals. However, only the 120-day islet and insulin implant groups maintained euglycemia (<200 mg/dl) following discontinuation of insulin treatment. The beta-cell was significantly increased in all the 120 day insulin-treated groups (insulin implant, 0.69+/-0.23 mg; and islet transplant, 0.91+/-0.23 mg) compared non-diabetic control mice (1.54+/-0.25 mg). We also show that we can use bioluminescent imaging to monitor beta-cell regeneration in living MIP-luc transgenic mice.

Conclusions/significance: The results show that insulin treatment can promote beta-cell regeneration. Moreover, the extent of restoration of beta-cell function and mass depend on the length of treatment period and overall level of glycemic control with better control being associated with improved recovery. Finally, real-time bioluminescent imaging can be used to monitor beta-cell recovery in living MIP-luc transgenic mice.

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Related in: MedlinePlus

Bioluminescence and Glycemic Control in Streptozotocin-induced Diabetic MIP-luc Mice.A. Representative bioluminescent images of five MIP-luc transgenic mice made diabetic with STZ and insulin treated by islet transplant under the kidney capsule. B. Bioluminescent signal (photons/sec) during the treatment phase. C. Blood glucose levels during the treatment (120 days) phase.
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pone-0008749-g003: Bioluminescence and Glycemic Control in Streptozotocin-induced Diabetic MIP-luc Mice.A. Representative bioluminescent images of five MIP-luc transgenic mice made diabetic with STZ and insulin treated by islet transplant under the kidney capsule. B. Bioluminescent signal (photons/sec) during the treatment phase. C. Blood glucose levels during the treatment (120 days) phase.

Mentions: STZ-induced diabetic MIP-luc female mice (C57BL/6 background) were treated with 200 syngeneic wild-type C57BL/6 islets placed under the kidney capsule. The transplanted islets do not express the MIP-luc transgene, and consequently, the bioluminescent signal reflects the endogenous beta-cell mass. The transplanted islets were removed at 120 days via nephrectomy beta-cell function monitored for an additional 30 days. The baseline bioluminescent signal was similar for all five MIP-luc mice. After STZ-induced diabetes, bioluminescence decreased continued to do so, reaching a nadir approximately 60 days after the induction of diabetes in all five mice (Fig. 3). After 60 days post-STZ treatment phase, four of the five mice (M1, M3, M9 and M12) showed a persistent increase in bioluminescent signal. In contrast, M2 demonstrated a transient increase in bioluminescent that eventually was lost. At 120 days post-STZ treatment, the bioluminescent signal of M1, M3, M9, and M12 showed a 5.2±1.5 fold increase compared to their nadir while M2, did not.


Glycemic control promotes pancreatic beta-cell regeneration in streptozotocin-induced diabetic mice.

Grossman EJ, Lee DD, Tao J, Wilson RA, Park SY, Bell GI, Chong AS - PLoS ONE (2010)

Bioluminescence and Glycemic Control in Streptozotocin-induced Diabetic MIP-luc Mice.A. Representative bioluminescent images of five MIP-luc transgenic mice made diabetic with STZ and insulin treated by islet transplant under the kidney capsule. B. Bioluminescent signal (photons/sec) during the treatment phase. C. Blood glucose levels during the treatment (120 days) phase.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2807460&req=5

pone-0008749-g003: Bioluminescence and Glycemic Control in Streptozotocin-induced Diabetic MIP-luc Mice.A. Representative bioluminescent images of five MIP-luc transgenic mice made diabetic with STZ and insulin treated by islet transplant under the kidney capsule. B. Bioluminescent signal (photons/sec) during the treatment phase. C. Blood glucose levels during the treatment (120 days) phase.
Mentions: STZ-induced diabetic MIP-luc female mice (C57BL/6 background) were treated with 200 syngeneic wild-type C57BL/6 islets placed under the kidney capsule. The transplanted islets do not express the MIP-luc transgene, and consequently, the bioluminescent signal reflects the endogenous beta-cell mass. The transplanted islets were removed at 120 days via nephrectomy beta-cell function monitored for an additional 30 days. The baseline bioluminescent signal was similar for all five MIP-luc mice. After STZ-induced diabetes, bioluminescence decreased continued to do so, reaching a nadir approximately 60 days after the induction of diabetes in all five mice (Fig. 3). After 60 days post-STZ treatment phase, four of the five mice (M1, M3, M9 and M12) showed a persistent increase in bioluminescent signal. In contrast, M2 demonstrated a transient increase in bioluminescent that eventually was lost. At 120 days post-STZ treatment, the bioluminescent signal of M1, M3, M9, and M12 showed a 5.2±1.5 fold increase compared to their nadir while M2, did not.

Bottom Line: Defining the conditions that promote beta-cell proliferation could benefit patients with diabetes.The results show that insulin treatment can promote beta-cell regeneration.Moreover, the extent of restoration of beta-cell function and mass depend on the length of treatment period and overall level of glycemic control with better control being associated with improved recovery.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, The University of Chicago, Chicago, Illinois, United States of America. eric.grossman@uchospitals.edu

ABSTRACT

Background: Pancreatic beta-cells proliferate following administration of the beta-cell toxin streptozotocin. Defining the conditions that promote beta-cell proliferation could benefit patients with diabetes. We have investigated the effect of insulin treatment on pancreatic beta-cell regeneration in streptozotocin-induced diabetic mice, and, in addition, report on a new approach to quantify beta-cell regeneration in vivo.

Methodology/principal findings: Streptozotocin-induced diabetic were treated with either syngeneic islets transplanted under the kidney capsule or subcutaneous insulin implants. After either 60 or 120 days of insulin treatment, the islet transplant or insulin implant were removed and blood glucose levels monitored for 30 days. The results showed that both islet transplants and insulin implants restored normoglycemia in the 60 and 120 day treated animals. However, only the 120-day islet and insulin implant groups maintained euglycemia (<200 mg/dl) following discontinuation of insulin treatment. The beta-cell was significantly increased in all the 120 day insulin-treated groups (insulin implant, 0.69+/-0.23 mg; and islet transplant, 0.91+/-0.23 mg) compared non-diabetic control mice (1.54+/-0.25 mg). We also show that we can use bioluminescent imaging to monitor beta-cell regeneration in living MIP-luc transgenic mice.

Conclusions/significance: The results show that insulin treatment can promote beta-cell regeneration. Moreover, the extent of restoration of beta-cell function and mass depend on the length of treatment period and overall level of glycemic control with better control being associated with improved recovery. Finally, real-time bioluminescent imaging can be used to monitor beta-cell recovery in living MIP-luc transgenic mice.

Show MeSH
Related in: MedlinePlus