char = I;code = 73
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
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char = d;code = 100
char = e;code = 101
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char = x;code = 120
char = y;code = 121
char = h;code = 104
char = y;code = 121
char = p;code = 112
char = u;code = 117
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = y;code = 121
char = n;code = 110
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = l;code = 108
char = e;code = 101
char = t;code = 116
char = ;code = 32
char = {;code = 123
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char = e;code = 101
char = t;code = 116
char = a;code = 97
char = };code = 125
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = f;code = 102
char = u;code = 117
char = n;code = 110
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = v;code = 118
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = t;code = 116
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = o;code = 111
char = p;code = 112
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = u;code = 117
char = m;code = 109
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = y;code = 121
char = p;code = 112
char = e;code = 101
char = ;code = 32
char = 2;code = 50
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = .;code = 46
result sql = Inhibition of deoxyhypusine synthase enhances islet {beta} cell function and survival in the setting of endoplasmic reticulum stress and type 2 diabetes.
Inhibition of deoxyhypusine synthase enhances islet {beta} cell function and survival in the setting of endoplasmic reticulum stress and type 2 diabetes.
char = I;code = 73
char = s;code = 115
char = l;code = 108
char = e;code = 101
char = t;code = 116
char = ;code = 32
char = &;code = 38
char = #;code = 35
char = 9;code = 57
char = 4;code = 52
char = 6;code = 54
char = ;;code = 59
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = d;code = 100
char = y;code = 121
char = s;code = 115
char = f;code = 102
char = u;code = 117
char = n;code = 110
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = f;code = 102
char = l;code = 108
char = a;code = 97
char = m;code = 109
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = E;code = 69
char = R;code = 82
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
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char = ;code = 32
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char = d;code = 100
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char = a;code = 97
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char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = k;code = 107
char = e;code = 101
char = y;code = 121
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
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char = o;code = 111
char = n;code = 110
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = ;code = 32
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 = r;code = 114
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = y;code = 121
char = p;code = 112
char = e;code = 101
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char = 2;code = 50
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = u;code = 117
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = t;code = 116
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = r;code = 114
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char = c;code = 99
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char = n;code = 110
char = t;code = 116
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
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char = e;code = 101
char = n;code = 110
char = z;code = 122
char = y;code = 121
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char = e;code = 101
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char = d;code = 100
char = e;code = 101
char = o;code = 111
char = x;code = 120
char = y;code = 121
char = h;code = 104
char = y;code = 121
char = p;code = 112
char = u;code = 117
char = s;code = 115
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char = n;code = 110
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = y;code = 121
char = n;code = 110
char = t;code = 116
char = h;code = 104
char = a;code = 97
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char = e;code = 101
char = ;code = 32
char = (;code = 40
char = D;code = 68
char = H;code = 72
char = S;code = 83
char = );code = 41
char = ;code = 32
char = p;code = 112
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char = m;code = 109
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char = s;code = 115
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char = e;code = 101
char = a;code = 97
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char = l;code = 108
char = y;code = 121
char = ;code = 32
char = c;code = 99
char = y;code = 121
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char = o;code = 111
char = k;code = 107
char = i;code = 105
char = n;code = 110
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char = u;code = 117
char = c;code = 99
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char = d;code = 100
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char = i;code = 105
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char = f;code = 102
char = l;code = 108
char = a;code = 97
char = m;code = 109
char = m;code = 109
char = a;code = 97
char = t;code = 116
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char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = &;code = 38
char = #;code = 35
char = 9;code = 57
char = 4;code = 52
char = 6;code = 54
char = ;;code = 59
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = .;code = 46
char = ;code = 32
char = D;code = 68
char = H;code = 72
char = S;code = 83
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = a;code = 97
char = l;code = 108
char = y;code = 121
char = z;code = 122
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = o;code = 111
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char = ;code = 32
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char = s;code = 115
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = h;code = 104
char = y;code = 121
char = p;code = 112
char = u;code = 117
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = e;code = 101
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char = ;code = 32
char = a;code = 97
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char = ;code = 32
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = n;code = 110
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char = ;code = 32
char = a;code = 97
char = c;code = 99
char = i;code = 105
char = d;code = 100
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char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = u;code = 117
char = n;code = 110
char = i;code = 105
char = q;code = 113
char = u;code = 117
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = e;code = 101
char = l;code = 108
char = o;code = 111
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char = g;code = 103
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = ;code = 32
char = f;code = 102
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = e;code = 101
char = I;code = 73
char = F;code = 70
char = 5;code = 53
char = A;code = 65
char = .;code = 46
char = ;code = 32
char = H;code = 72
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ,;code = 44
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char = w;code = 119
char = e;code = 101
char = ;code = 32
char = s;code = 115
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char = u;code = 117
char = g;code = 103
char = h;code = 104
char = t;code = 116
char = ;code = 32
char = t;code = 116
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char = m;code = 109
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char = w;code = 119
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char = e;code = 101
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = ;code = 32
char = D;code = 68
char = H;code = 72
char = S;code = 83
char = ;code = 32
char = a;code = 97
char = c;code = 99
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char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = c;code = 99
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char = r;code = 114
char = i;code = 105
char = b;code = 98
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char = t;code = 116
char = e;code = 101
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char = ;code = 32
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char = 4;code = 52
char = 6;code = 54
char = ;;code = 59
char = ;code = 32
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char = 6;code = 54
char = ;;code = 59
char = ;code = 32
char = c;code = 99
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char = l;code = 108
char = l;code = 108
char = ;code = 32
char = l;code = 108
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char = c;code = 99
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char = C;code = 67
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char = H;code = 72
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char = i;code = 105
char = b;code = 98
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char = G;code = 71
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char = 7;code = 55
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char = r;code = 114
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char = m;code = 109
char = i;code = 105
char = c;code = 99
char = ;code = 32
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char = l;code = 108
char = o;code = 111
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char = z;code = 122
char = a;code = 97
char = t;code = 116
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char = o;code = 111
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char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
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char = F;code = 70
char = 5;code = 53
char = A;code = 65
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = t;code = 116
char = h;code = 104
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char = E;code = 69
char = R;code = 82
char = ,;code = 44
char = ;code = 32
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char = b;code = 98
char = l;code = 108
char = y;code = 121
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char = e;code = 101
char = c;code = 99
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char = i;code = 105
char = n;code = 110
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char = a;code = 97
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char = i;code = 105
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char = o;code = 111
char = f;code = 102
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char = F;code = 70
char = 5;code = 53
char = A;code = 65
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char = i;code = 105
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char = b;code = 98
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char = s;code = 115
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char = e;code = 101
char = ;code = 32
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char = ;code = 32
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char = i;code = 105
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char = r;code = 114
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char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = C;code = 67
char = H;code = 72
char = O;code = 79
char = P;code = 80
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
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char = e;code = 101
char = s;code = 115
char = p;code = 112
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = E;code = 69
char = R;code = 82
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = &;code = 38
char = #;code = 35
char = 9;code = 57
char = 4;code = 52
char = 6;code = 54
char = ;;code = 59
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
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char = b;code = 98
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char = /;code = 47
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result sql = Islet β cell dysfunction resulting from inflammation, ER stress, and oxidative stress is a key determinant in the progression from insulin resistance to type 2 diabetes mellitus. It was recently shown that the enzyme deoxyhypusine synthase (DHS) promotes early cytokine-induced inflammation in the β cell. DHS catalyzes the conversion of lysine to hypusine, an amino acid that is unique to the translational elongation factor eIF5A. Here, we sought to determine whether DHS activity contributes to β cell dysfunction in models of type 2 diabetes in mice and β cell lines. A 2-week treatment of obese diabetic C57BLKS/J-db/db mice with the DHS inhibitor GC7 resulted in improved glucose tolerance, increased insulin release, and enhanced β cell mass. Thapsigargin treatment of β cells in vitro induces a picture of ER stress and apoptosis similar to that seen in db/db mice; in this setting, DHS inhibition led to a block in CHOP (CAAT/enhancer binding protein homologous protein) production despite >30-fold activation of Chop gene transcription. Blockage of CHOP translation resulted in reduction of downstream caspase-3 cleavage and near-complete protection of cells from apoptotic death. DHS inhibition appeared to prevent the cytoplasmic co-localization of eIF5A with the ER, possibly precluding the participation of eIF5A in translational elongation at ER-based ribosomes. We conclude that hypusination by DHS is required for the ongoing production of proteins, particularly CHOP, in response to ER stress in the β cell.

Publication: J. Biol. Chem. 2010 Dec 17 ;285(51)::39943-52. :doi: 10.1074/jbc.M110.170142.
Publication Date: 2010 Dec 17
Study Author(s): Robbins, Reiesha D;Tersey, Sarah A;Ogihara, Takeshi;Gupta, Dhananjay;Farb, Thomas B;Ficorilli, James;Bokvist, Krister;Maier, Bernhard;Mirmira, Raghavendra G;
Institution: Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22904, USA.
Shortcut link to this study:
Islet β cell dysfunction resulting from inflammation, ER stress, and oxidative stress is a key determinant in the progression from insulin resistance to type 2 diabetes mellitus. It was recently shown that the enzyme deoxyhypusine synthase (DHS) promotes early cytokine-induced inflammation in the β cell. DHS catalyzes the conversion of lysine to hypusine, an amino acid that is unique to the translational elongation factor eIF5A. Here, we sought to determine whether DHS activity contributes to β cell dysfunction in models of type 2 diabetes in mice and β cell lines. A 2-week treatment of obese diabetic C57BLKS/J-db/db mice with the DHS inhibitor GC7 resulted in improved glucose tolerance, increased insulin release, and enhanced β cell mass. Thapsigargin treatment of β cells in vitro induces a picture of ER stress and apoptosis similar to that seen in db/db mice; in this setting, DHS inhibition led to a block in CHOP (CAAT/enhancer binding protein homologous protein) production despite >30-fold activation of Chop gene transcription. Blockage of CHOP translation resulted in reduction of downstream caspase-3 cleavage and near-complete protection of cells from apoptotic death. DHS inhibition appeared to prevent the cytoplasmic co-localization of eIF5A with the ER, possibly precluding the participation of eIF5A in translational elongation at ER-based ribosomes. We conclude that hypusination by DHS is required for the ongoing production of proteins, particularly CHOP, in response to ER stress in the β cell.
PMID: 20956533

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