Unusual case of neonatal diabetes mellitus due to congenital pancreas agenesis.

Congenital absence of the pancreas is an extremely rare condition. We participated in the care of a patient with an unusual presentation of neonatal diabetes attributable to agenesis of the pancreas. Additional clinical features of the patient included cardiac septal defects, gall bladder agenesis and duodenal malrotation.

The Pal elements in the upstream glucokinase promoter exhibit dyad symmetry and display cell-specific enhancer activity when multimerised.

Aims/hypothesis: The upstream glucokinase (betaGK) promoter has previously been shown to contain two 9-bp sequences, termed the Pal motifs, that are conserved in humans, rats and mice. These motifs are necessary for expression of the betaGK promoter in pancreatic beta cell lines and pituitary corticotrope cell lines. DNA probes containing the Pal motifs bind cell-type-specific protein complexes, but these motifs have not been completely characterised.

BETA2 activates transcription from the upstream glucokinase gene promoter in islet beta-cells and gut endocrine cells.

Glucokinase (GK) gene transcription initiates in the islet (beta-cell), gut, and brain from promoter sequences residing approximately 35 kbp upstream from those used in liver. Expression of betaGK is controlled in beta-cells by cell-enriched (i.e.

Dual roles for glucokinase in glucose homeostasis as determined by liver and pancreatic beta cell-specific gene knock-outs using Cre recombinase.

Glucokinase (GK) gene mutations cause diabetes mellitus in both humans and mouse models, but the pathophysiological basis is only partially defined. We have used cre-loxP technology in combination with gene targeting to perform global, beta cell-, and hepatocyte-specific gene knock-outs of this enzyme in mice. Gene targeting was used to create a triple-loxed gk allele, which was converted by partial or total Cre-mediated recombination to a conditional allele lacking neomycin resistance, or to a null allele, respectively.

Activation of glycine and glutamate receptors increases intracellular calcium in cells derived from the endocrine pancreas.

We studied calcium signaling in a newly described pancreatic cell line, GK-P3, that expresses functional amino acid neurotransmitter receptors. GK-P3 cells express the first strychnine-sensitive glycine receptors reported in a permanent cell line. In addition, GK-P3 cells express alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors.

Targeted oncogenesis of hormone-negative pancreatic islet progenitor cells.

Transgenic mice containing an upstream glucokinase (betaGK) promoter- simian virus 40 T antigen (Tag) fusion gene develop neuroendocrine tumors primarily in the pancreas, gut, and pituitary. Pancreatic tumors from a line with delayed tumorigenesis were of two different types: insulinomas and noninsulinomas. The noninsulinomas are often periductal in location, express none of the four major islet peptide hormones, Glut-2, Pdx1, tyrosine hydroxylase, Pax4, Pax6, or Nkx6.

Variable expression of hepatic glucokinase in mice is due to a regulational locus that cosegregates with the glucokinase gene.

The Gk activity locus affects expression of hepatic glucokinase (GK) in mice. Analysis of microsatellites within the mouse GK gene locus revealed two major haplotypes in 19 of 22 inbred strains predictive of either high or low hepatic GK gene expression. C3H/HeJ mice, a high-activity strain, and two other wild-derived strains contain less common haplotypes.

Characterization of the Pal motifs in the upstream glucokinase promoter: binding of a cell type-specific protein complex correlates with transcriptional activation.

The upstream glucokinase (GK) promoter is expressed specifically in several different neural/neuroendocrine (NE) cell types, including the pancreatic beta-cell and pituitary corticotrope. Previously, a mutational and evolutionary analysis of this promoter identified two identical 9-bp motifs (TGGTCACCA) termed Pal-1 and Pal-2 that are essential for high level expression in HIT M2.2.

Thyroid hormone inhibition of human thyrotropin beta-subunit gene expression is mediated by a cis-acting element located in the first exon.

Thyroid hormone regulation of the human thyrotropin beta-subunit gene (TSH beta) was examined in a human embryonal cell line (293). Transient expression studies were performed with chimeric plasmids containing the reporter gene, chloramphenicol acetyltransferase. Sequences in the first exon between +9 and +37 base pairs (bp) enhanced gene expression from the human TSH beta promoter in the absence of thyroid hormone as well as mediated a concentration-dependent triiodothyronine (L-T3) decrease in gene expression.

Metabolic role of the exercise-induced increment in epinephrine in the dog.

The role of the exercise-induced increment in epinephrine was studied in five adrenalectomized (ADX) and in six normal dogs (C). Experiments consisted of an 80-min equilibration period, a 40-min basal period, and a 150-min exercise period. ADX were studied with epinephrine replaced to basal levels during rest and to increased levels during exercise to simulate its normal rise (HE) and on a separate day with epinephrine maintained at basal levels throughout the study (BE).

Isolation and characterization of the human thyrotropin beta-subunit gene. Differences in gene structure and promoter function from murine species.

The human thyrotropin beta-subunit gene was isolated and characterized from two genomic libraries and found to contain three exons separated by two introns of 3.9 and 0.45 kilobase pairs.