Glucose Tolerance Test (GTT) (A) and Insulin Tolerance Test (ITT) glycemia responses (B) increase in high fat diet-fed mice.

<p>Glycemia AUC, area under the curve (AUC) analysis of glycemia profile of GTT and ITT after eight weeks of diet regimen. Values are expressed as mean ± SEM (10–28 mice/group). * p < 0.05, control group (C) <i>vs</i>. high fat diet group (HFD).</p

Experimental groups and study design.

<p>Eight weeks after high fat-diet or standard diet regimen (control group), mice received 4 weekly intraperitoneal (i.p) infusions of PBS (HFD-PBS group) or 5–8 x 106 BM-MSC (HFD-MSC group). Fasting glycemia (FG) was determined every week and glucose (GTT) and insulin (ITT) tolerance tests were performed in the 9^th, 17^th, 21^st, 25^th, and 29^th week of the experimental period.</p

Glucose Tolerance Test (GTT) glycemia response decrease post-MSCs infusion.

<p>Only in the 16^th week post-MSC infusions, the glycemia response to glucose injection was significantly lower in HFD-MSCs-R when compared to HFD-PBS group. Values are expressed as mean ± SEM (5–13 mice/group). * p < 0.05, control group (C) <i>vs</i>. HFD-PBS; ^# p < 0.05, HFD-MSCs-R <i>vs</i>. HFD-PBS.</p

Fasting glycemia decrease post-MSCs infusion.

<p>Sixteen weeks after the 4^th infusion of BM-MSCs, 72.2% (n = 13) of the animals attained fasting glycemia lower than 180 mg/dL (responders). Post- infusion fasting glycemia of these mice was significantly lower than their pre-infusion values. * p < 0.05, pre-<i>vs</i>. post-infusion of BM-MSCs fasting glycemia.</p

Correlation analysis.

<p>Islet apoptosis was positively correlated with fasting glycemia (A) and glucose tolerance test (GTT) (B) and insulin tolerance test (ITT) glycemia responses (C). Islet proliferation was negatively correlated with fasting glycemia (D).</p

Relative volumes of islet α-cell decrease in HFD-PBS and increase in HFD-MSCs-NR.

<p>Representative images of pancreas section stained for glucagon of control group (A) and HFD-PBS (B), HFD-MSCs-R (C), and HFD-MSCs-NR (D) groups. Quantitative data correspond to mean ± SEM (5–13 mice/group) (E). * p < 0.05, control group (C) <i>vs</i>. HFD-PBS; ⁺ p < 0.05, HFD-MSCs-NR <i>vs</i>. HFD-PBS; ^& p < 0.05, HFD-MSCs-NR <i>vs</i>. HFD-MSCs-R.</p

Bone marrow-derived MSCs isolated from <i>Wistar</i> rats.

<p>Immunologic phenotypes of MSCs (A). Passage five plastic adherent cells cultured in alpha-MEM supplemented with 15% fetal bovine serum (B) and differentiated into adipogenic (C) or osteogenic (D) lineages.</p

Fasting glycemia decrease since the 7^th week post-MSCs infusion.

<p>Fasting glycemia of HFD-MSCs-R mice was significantly lower compared to HFD-PBS since the 7^th week post- MSC infusion. Values are expressed as mean ± SEM (5–13 mice/group). * p < 0.05, control group (C) <i>vs</i>. high fat diet group (HFD-PBS); ^# p < 0.05, HFD-MSCs-R <i>vs</i>. HFD-PBS.</p

Islet apoptosis increases in HFD-PBS and HFD-MSCs-NR and decreases in HFD-MSCs-R.

<p>Representative images of pancreas section stained for caspase-3 of control group (A) and HFD-PBS (B), HFD-MSCs-R (C), and HFD-MSCs-NR (D) groups. Quantitative data correspond to mean ± SEM (5–13 mice/group) (E). * p < 0.05, control group (C) <i>vs</i>. HFD-PBS; ^# p < 0.05, HFD-MSCs-R <i>vs</i>. HFD-PBS; ⁺ p < 0.05, HFD-MSCs-NR <i>vs</i>. HFD-PBS; ^& p < 0.05, HFD-MSCs-NR <i>vs</i>. HFD-MSCs-R.</p

Body Weight (g).

<p>Values are expressed as mean ± SEM (n = 5–13 mice/group).</p><p>*p < 0.05, HFD-PBS <i>vs</i>. C.</p><p>Body Weight (g).</p