scholarly journals Laron Dwarfism and Non-Insulin-Dependent Diabetes Mellitus in the Hnf-1α Knockout Mouse

1998 ◽  
Vol 18 (5) ◽  
pp. 3059-3068 ◽  
Author(s):  
Ying-Hue Lee ◽  
Brian Sauer ◽  
Frank J. Gonzalez
Keyword(s):  
Diabetes Mellitus ◽  
Elevated Serum ◽  
Insulin Dependent Diabetes Mellitus ◽  
Regulatory Elements ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Null Mouse ◽  
Recombination System ◽  
Igf I ◽  
Insulin Dependent

ABSTRACT Mice deficient in hepatocyte nuclear factor 1 alpha (HNF-1α) were produced by use of the Cre-loxP recombination system. HNF-1α-null mice are viable but sterile and exhibit a phenotype reminiscent of both Laron-type dwarfism and non-insulin-dependent diabetes mellitus (NIDDM). In contrast to an earlier HNF-1α-null mouse line that had been produced by use of standard gene disruption methodology (M. Pontoglio, J. Barra, M. Hadchouel, A. Doyen, C. Kress, J. P. Bach, C. Babinet, and M. Yaniv, Cell 84:575–585, 1996), these mice exhibited no increased mortality and only minimal renal dysfunction during the first 6 months of development. Both dwarfism and NIDDM are most likely due to the loss of expression of insulin-like growth factor I (IGF-I) and lower levels of insulin, resulting in stunted growth and elevated serum glucose levels, respectively. These results confirm the functional significance of the HNF-1α regulatory elements that had previously been shown to reside in the promoter regions of both the IGF-I and the insulin genes.

Insulin-like growth factor binding proteins in prepubertal children with insulin-dependent diabetes mellitus

1995 ◽  
Vol 133 (4) ◽  
pp. 440-444 ◽  
Author(s):  
Mikael Knip ◽  
Päivi Tapanainen ◽  
Fredrika Pekonen ◽  
Werner F Blum
Keyword(s):  
Diabetes Mellitus ◽  
Growth Factor ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Insulin Like Growth Factor ◽  
Prepubertal Children ◽  
Igf I ◽  
Diabetic Children ◽  
Insulin Dependent

Knip M, Tapanainen P, Pekonen F, Blum WF. Insulin-like growth factor binding proteins in prepubertal children with insulin-dependent diabetes mellitus. Eur J Endocrinol 1995:133:440–4. ISSN 0804–4643 To study the possible role of insulin-like growth factor binding proteins (IGFBPs) in the discrepancy between normal or only slightly retarded growth and substantially reduced concentrations of insulin-like growth factor I (IGF-I) in prepubertal children with insulin-dependent diabetes mellitus (IDDM), we measured the plasma concentrations of IGF-I, IGFBP-1, IGFBP-2 and IGFBP-3 and free insulin in 24 prepubertal diabetic subjects and 12 control children. In addition, the growth hormone response to exercise was evaluated. The diabetic children had significantly decreased peripheral IGF-I levels (8.2 + 1.1 (sem) vs 16.7 + 2.5 nmol/l; p < 0.001), whereas the concentrations of free insulin were increased (217 + 14 vs 103 + 21 pmol/l; p < 0.001). The concentrations of IGFBP-1 and IGFBP-3 were of the same magnitude in both groups. The diabetic children had significantly increased levels of IGFBP-2 (465 + 13 vs 416 + 14 μg/l; p = 0.029), which were inversely related to the circulating IGF-I levels (r = −0.35; p = 0.034). The diabetic and control children had comparable growth hormone responses to exercise. Diabetic children with poor glucose control had even lower IGF-I levels than those with moderate metabolic control (6.0 + 0.8 vs 10.3 + 1.7 nmol/l; p = 0.037). No differences could be observed in the plasma concentrations of various IGFBPs between these two groups of diabetic subjects. The absence in prepubertal diabetic children of increased IGFBP-1 levels observed in adolescent and adult patients with IDDM may contribute to their maintained linear growth, despite definitely decreased IGF-I concentrations. The role of increased IGFBP-2 levels in prepubertal children with IDDM remains open, but the inverse relationship between IGF-I levels and IGFBP-2 concentrations suggests that IGF-I may be involved in the regulation of IGFBP-2. Mikael Knip, Department of Pediatrics, University of Oulu, FIN-90220 Oulu, Finland

Effect of one year continuous subcutaneous infusion of a somatostatin analogue, octreotide, on early retinopathy, metabolic control and thyroid function in Type I (insulin-dependent) diabetes mellitus

1990 ◽  
Vol 122 (6) ◽  
pp. 766-772 ◽  
Author(s):  
Carsten Kirkegaard ◽  
Kirsten Nørgaard ◽  
Ole Snorgaard ◽  
Toke Bek ◽  
Michael Larsen ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Fundus Photography ◽  
Dependent Diabetes Mellitus ◽  
Type I ◽  
Igf I ◽  
Insulin Dependent ◽  
One Year ◽  
Analogue Octreotide

Abstract. Growth hormone is assumed to be involved in the development of diabetic retinopathy. In a randomized study we evaluated the possible effects of one year treatment with a somatostatin (SRIH) analogue, octreotide, on early retinopathy and on metabolism in Type I (insulin-dependent) diabetes mellitus. Eleven patients were allocated to treatment with a continuous sc infusion of 400 μg octreotide per day and 9 served as controls. Only 7 patients from each group completed the study. Three octreotide-treated patients left the study owing to severe diarrhea. The subjects were evaluated at entry, after 2, 6 and 12 months treatment, and 2 months after withdrawal. Octreotide induced a decrease in GH secretion, expressed as the area under the 24 h serum GH profiles (p<0.05), and of the serum levels of IGF-I (p<0.05). The entire decline in GH levels occurred during the daytime, whereas the nocturnal levels were unaffected. Retinopathy, as assessed by determination of the blood retina barrier permeability, by colour fundus photography, and flurescein angiography was unchanged in both groups. Apart from a decline in insulin requirements, octreotide had no major effect on glycemic control, but induced a mild transient pituitary hypothyroidism, not clinically relevant. We conclude that treatment with octreotide for one year has modest effects on GH, IGF-I, and glucose metabolism, but has no significant effect on early retinopathy in Type I (insulin-dependent) diabetes.

Elevated serum and urinary thrombomodulin levels in patients with non-insulin-dependent diabetes mellitus

1994 ◽  
Vol 225 (2) ◽  
pp. 89-96 ◽  
Author(s):  
Hitoshi Shimano ◽  
Keiichi Takahashi ◽  
Masanobu Kawakami ◽  
Takanari Gotoda ◽  
Kenji Harada ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Elevated Serum ◽  
Insulin Dependent Diabetes Mellitus ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Insulin Dependent
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