Table 1.
Summary of genetic mouse models used to identify in vivo roles of TGFβ signaling in glucose homeostasis.
| MOUSE MODEL | PHENOTYPE | REFERENCE |
|---|---|---|
| ACTIVIN: | ||
| ActRIIA and IIB knock out | Hypoplastic islets, impaired glucose tolerance |
[13] |
| ActRIIB knock out | Hypoplastic islets | [22] |
| Double ActRIIB/Smad 2 heterozygotes | Hypoplastic islets, decreased islet area, decreased insulin content, impaired glucose tolerance |
[22] |
| Dominant negative Activin Type IIR | β-cell hypoplasia, impaired glucose tolerance |
[12,23] |
| Activin B knock out | Hyperinsulinemia | [17] |
| ALK7 knock out | Hyperinsulinemia, decreased insulin sensitivity, impaired glucose tolerance, enlarged islets |
[17] |
| TGF-β: | ||
| Transgenic overexpression of TGF-β through insulin promoter |
Decreased development of exocrine pancreas and islets, maintenance of glucose control |
[41,42] |
| Transgenic overexpresssion of TGF-β through glucagon promoter |
B-cell hypoplasia, decreased insulin secretion, impaired glucose tolerance |
[43] |
| MYOSTATIN: | ||
| Myostatin knock out | Increase in skeletal muscle mass, decrease in fat mass, increased glucose utilization, increased insulin sensitivity |
[46-48] |
| GDF11: | ||
| GDF11 knock out | Increase in NGN+ islet precursor cells that did not develop into mature β-cells |
[45] |
| BMP: | ||
| Transgenic overexpression of BMP4 | Increased glucose tolerance, increased insulin secretion |
[49] |
| ALK3 knock out | Impaired glucose tolerance, diabetes | [49] |
| FSTL3: | ||
| FSTL3 knock out | Enlarged islets, β-cell hyperplasia, increased glucose tolerance, slight hyperinsulinemia |
[53] |
| SMAD 2: | ||
| Smad 2 heterozygote | Hypoplastic islets | [22] |
| Smad 2 conditional mice | Increase in NGN+ cells and decreased β-cell mass |
[45] |
| SMAD 3: | ||
| Smad 3 knock out | Increased insulin production and release, enhanced glucose tolerance, no change in β-cell mass |
[40] |
| SMAD 6: | ||
| Transgenic overexpression of noggin and Smad 6 |
Impaired glucose tolerance, diabetes | [49] |
| SMAD 7: | ||
| Conditional transgenic overexpression of Smad 7 |
Hypoplastic islets, decreased insulin content, impaired glucose tolerance, increased serum glucose (reversible condition by removal of the Smad7 overexpression) |
[44] |