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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

Representative pancreatic islets showing insulin staining (brown) in untreated STZ-diabetic mice, non-diabetic control and STZ-diabetic mice treated with insulin implants or islet transplant (txp) under the kidney capsule for 60 or 120 days (40x).
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pone-0008749-g002: Representative pancreatic islets showing insulin staining (brown) in untreated STZ-diabetic mice, non-diabetic control and STZ-diabetic mice treated with insulin implants or islet transplant (txp) under the kidney capsule for 60 or 120 days (40x).

Mentions: There was no significant increase in beta-cell mass in the 60-day-insulin-treated groups compared to STZ-treated controls (untreated STZ-control group, 0.09±0.01 mg; islet transplant, 0.14±0.09 mg; and insulin implant, 0.18±0.13 mg) (Table 2). In contrast, there was a significant increase in beta-cell mass in both the 120-day-insulin-treated groups compared to untreated STZ-induced diabetic mice (islet transplant, 0.91±0.23 mg; insulin implant, 0.69±0.22 mg). The maximum beta-cell regeneration occurred in the 120-day islet transplant group achieving a 60% recovery of beta-cell mass that was statistically greater than the 45% recovery in 120-day insulin implant group (P<0.05). The islets from the 120-day islet transplant group were large and densely populated with insulin-producing beta-cells as compared to the other treatment groups (Fig. 2).


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)

Representative pancreatic islets showing insulin staining (brown) in untreated STZ-diabetic mice, non-diabetic control and STZ-diabetic mice treated with insulin implants or islet transplant (txp) under the kidney capsule for 60 or 120 days (40x).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0008749-g002: Representative pancreatic islets showing insulin staining (brown) in untreated STZ-diabetic mice, non-diabetic control and STZ-diabetic mice treated with insulin implants or islet transplant (txp) under the kidney capsule for 60 or 120 days (40x).
Mentions: There was no significant increase in beta-cell mass in the 60-day-insulin-treated groups compared to STZ-treated controls (untreated STZ-control group, 0.09±0.01 mg; islet transplant, 0.14±0.09 mg; and insulin implant, 0.18±0.13 mg) (Table 2). In contrast, there was a significant increase in beta-cell mass in both the 120-day-insulin-treated groups compared to untreated STZ-induced diabetic mice (islet transplant, 0.91±0.23 mg; insulin implant, 0.69±0.22 mg). The maximum beta-cell regeneration occurred in the 120-day islet transplant group achieving a 60% recovery of beta-cell mass that was statistically greater than the 45% recovery in 120-day insulin implant group (P<0.05). The islets from the 120-day islet transplant group were large and densely populated with insulin-producing beta-cells as compared to the other treatment groups (Fig. 2).

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