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result sql = Inhibition of DPP-4 with sitagliptin improves glycemic control and restores islet cell mass and function in a rodent model of type 2 diabetes.
Inhibition of DPP-4 with sitagliptin improves glycemic control and restores islet cell mass and function in a rodent model of type 2 diabetes.
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char = p;code = 112
char = t;code = 116
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char = ;code = 32
char = I;code = 73
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = o;code = 111
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char = t;code = 116
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char = p;code = 112
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char = z;code = 122
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char = i;code = 105
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char = e;code = 101
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char = c;code = 99
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char = r;code = 114
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char = n;code = 110
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char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = l;code = 108
char = y;code = 121
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char = w;code = 119
char = e;code = 101
char = e;code = 101
char = k;code = 107
char = s;code = 115
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char = a;code = 97
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char = ;code = 32
char = t;code = 116
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char = a;code = 97
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char = e;code = 101
char = s;code = 115
char = s;code = 115
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char = e;code = 101
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char = r;code = 114
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char = e;code = 101
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char = c;code = 99
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char = m;code = 109
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = a;code = 97
char = g;code = 103
char = l;code = 108
char = i;code = 105
char = p;code = 112
char = t;code = 116
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char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = a;code = 97
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char = ;code = 32
char = h;code = 104
char = a;code = 97
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char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
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char = o;code = 111
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = i;code = 105
char = r;code = 114
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = g;code = 103
char = l;code = 108
char = u;code = 117
char = c;code = 99
char = a;code = 97
char = g;code = 103
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = s;code = 115
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char = o;code = 111
char = r;code = 114
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char = g;code = 103
char = l;code = 108
char = u;code = 117
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = v;code = 118
char = e;code = 101
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = g;code = 103
char = l;code = 108
char = y;code = 121
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char = e;code = 101
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char = i;code = 105
char = c;code = 99
char = ;code = 32
char = c;code = 99
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char = n;code = 110
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = a;code = 97
char = g;code = 103
char = l;code = 108
char = i;code = 105
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = -;code = 45
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = e;code = 101
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char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = s;code = 115
char = o;code = 111
char = c;code = 99
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = a;code = 97
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char = t;code = 116
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char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = g;code = 103
char = l;code = 108
char = u;code = 117
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = e;code = 101
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char = d;code = 100
char = e;code = 101
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char = e;code = 101
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char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
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char = i;code = 105
char = n;code = 110
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = s;code = 115
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char = c;code = 99
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char = t;code = 116
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char = i;code = 105
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char = a;code = 97
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char = l;code = 108
char = e;code = 101
char = t;code = 116
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = m;code = 109
char = p;code = 112
char = o;code = 111
char = r;code = 114
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char = t;code = 116
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char = a;code = 97
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char = t;code = 116
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char = f;code = 102
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char = ;code = 32
char = s;code = 115
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char = t;code = 116
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char = l;code = 108
char = i;code = 105
char = p;code = 112
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char = s;code = 115
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char = g;code = 103
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char = f;code = 102
char = i;code = 105
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char = p;code = 112
char = h;code = 104
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char = s;code = 115
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char = a;code = 97
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char = w;code = 119
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char = a;code = 97
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char = l;code = 108
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = e;code = 101
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char = d;code = 100
char = a;code = 97
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char = i;code = 105
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char = c;code = 99
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char = t;code = 116
char = h;code = 104
char = a;code = 97
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char = D;code = 68
char = P;code = 80
char = P;code = 80
char = -;code = 45
char = 4;code = 52
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char = i;code = 105
char = n;code = 110
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char = i;code = 105
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char = t;code = 116
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char = t;code = 116
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char = i;code = 105
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char = i;code = 105
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char = e;code = 101
char = r;code = 114
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char = l;code = 108
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char = t;code = 116
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char = y;code = 121
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char = a;code = 97
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char = i;code = 105
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char = a;code = 97
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char = o;code = 111
char = d;code = 100
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char = .;code = 46
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char = T;code = 84
char = h;code = 104
char = e;code = 101
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char = a;code = 97
char = b;code = 98
char = i;code = 105
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char = a;code = 97
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char = l;code = 108
char = i;code = 105
char = p;code = 112
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char = a;code = 97
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char = i;code = 105
char = s;code = 115
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char = c;code = 99
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char = a;code = 97
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char = f;code = 102
char = f;code = 102
char = e;code = 101
char = r;code = 114
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char = i;code = 105
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char = g;code = 103
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char = t;code = 116
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char = o;code = 111
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char = p;code = 112
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char = e;code = 101
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char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
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char = d;code = 100
char = i;code = 105
char = s;code = 115
char = e;code = 101
char = a;code = 97
char = s;code = 115
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char = m;code = 109
char = o;code = 111
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char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
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char = o;code = 111
char = n;code = 110
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
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result sql = Inhibition of dipeptidyl peptidase-4 (DPP-4) activity has been shown to improve glycemic control in patients with type 2 diabetes by prolonging and potentiating the actions of incretin hormones. This study is designed to determine the effects of the DPP-4 inhibitor sitagliptin on improving islet function in a mouse model of insulin resistance and insulin secretion defects. ICR mice were pre-treated with high fat diet and a low dose of streptozotocin to induce insulin resistance and impaired insulin secretion, respectively. Diabetic mice were treated with sitagliptin or the sulfonylurea agent glipizide as admixture to high fat diet for ten weeks. Sustained reduction of blood glucose, HbA(1c), circulating glucagon and improvement in oral glucose tolerance were observed in mice treated with sitagliptin. In contrast, glipizide improved glycemic control only during the early weeks and to a lesser degree compared to sitagliptin, and had no effect on circulating glucagon levels or glucose tolerance. The improvement in glycemic control in sitagliptin-treated mice was associated with a significant increase in glucose-dependent insulin secretion in both perfused pancreas and isolated islets. Importantly, in contrast to the lack of effect by glipizide, sitagliptin significantly restored beta and alpha cell mass as well as alpha/beta cell ratio. These data indicate that DPP-4 inhibition by sitagliptin provided better overall improvement of glycemic control compared to glipizide in the high fat diet/streptozotocin induced diabetic mouse model. The ability of sitagliptin to enhance islet cell function may offer insight into the potential for disease modification.

Publication: Eur. J. Pharmacol. 2009 Nov 25 ;623(1-3)::148-54. :doi: 10.1016/j.ejphar.2009.09.027.
Publication Date: 2009 Nov 25
Study Author(s): Mu, James;Petrov, Aleksandr;Eiermann, George J;Woods, John;Zhou, Yun-Ping;Li, Zhihua;Zycband, Emanuel;Feng, Yue;Zhu, Lan;Roy, Ranabir Sinha;Howard, Andrew D;Li, Cai;Thornberry, Nancy A;Zhang, Bei B;
Institution: Department of Metabolic Disorders, Merck Research Laboratories, Rahway, NJ 07065, USA. [email protected]
Shortcut link to this study:
Inhibition of dipeptidyl peptidase-4 (DPP-4) activity has been shown to improve glycemic control in patients with type 2 diabetes by prolonging and potentiating the actions of incretin hormones. This study is designed to determine the effects of the DPP-4 inhibitor sitagliptin on improving islet function in a mouse model of insulin resistance and insulin secretion defects. ICR mice were pre-treated with high fat diet and a low dose of streptozotocin to induce insulin resistance and impaired insulin secretion, respectively. Diabetic mice were treated with sitagliptin or the sulfonylurea agent glipizide as admixture to high fat diet for ten weeks. Sustained reduction of blood glucose, HbA(1c), circulating glucagon and improvement in oral glucose tolerance were observed in mice treated with sitagliptin. In contrast, glipizide improved glycemic control only during the early weeks and to a lesser degree compared to sitagliptin, and had no effect on circulating glucagon levels or glucose tolerance. The improvement in glycemic control in sitagliptin-treated mice was associated with a significant increase in glucose-dependent insulin secretion in both perfused pancreas and isolated islets. Importantly, in contrast to the lack of effect by glipizide, sitagliptin significantly restored beta and alpha cell mass as well as alpha/beta cell ratio. These data indicate that DPP-4 inhibition by sitagliptin provided better overall improvement of glycemic control compared to glipizide in the high fat diet/streptozotocin induced diabetic mouse model. The ability of sitagliptin to enhance islet cell function may offer insight into the potential for disease modification.
PMID: 19765579

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