[Abstract unavailable

Type 2 or non-insulin-dependent diabetes mellitus (NIDDM) is the most common form of diabetes worldwide, affecting approximately 4% of the world's adult population. It is multifactorial in origin with both genetic and environmental factors contributing to its development. A genome-wide screen for type 2 diabetes genes carried out in Mexican Americans localized a susceptibility gene, designated NIDDM1, to chromosome 2. Here we describe the positional cloning of a gene located in the NIDDM1 region that shows association with type 2 diabetes in Mexican Americans and a Northern European population from the Botnia region of Finland. This putative diabetes-susceptibility gene encodes a ubiquitously expressed member of the calpain-like cysteine protease family, calpain-10 (CAPN10). This finding suggests a novel pathway that may contribute to the development of type 2 diabetes.

Calcium plays a critical part in the regulation of cell growth, and growth factors stimulate calcium entry into cells through calcium-permeable channels. However, the molecular nature and regulation of calcium-permeable channels are still unclear at present. Here we report the molecular characterization of a calcium-permeable cation channel that is regulated by insulin-like growth factor-I (IGF-I). This channel, which we name growth-factor-regulated channel (GRC), belongs to the TRP-channel family and localizes mainly to intracellular pools under basal conditions. Upon stimulation of cells by IGF-I, GRC translocates to the plasma membrane. Thus, IGF-I augments calcium entry through GRC by regulating trafficking of the channel.

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Abstract:We have isolated a human cDNA encoding a protein, designated DNPI, that shows 82% amino acid identity and 92% similarity to the human brain-specific Na ϩ -dependent inorganic phosphate (Na ϩ /P i ) cotransporter (BNPI), which is localized exclusively to neuron-rich regions. Expression of DNPI mRNA in Xenopus oocytes resulted in a significant increase in Na ϩ -dependent P i transport, indicating that DNPI is a novel Na ϩ /P i cotransporter. Northern blot analysis shows that DNPI mRNA is expressed predominantly in brain, where the highest levels are observed in medulla, substantia nigra, subthalamic nucleus, and thalamus, all of which express BNPI mRNA at low levels. In contrast, DNPI mRNA is expressed at low levels in cerebellum and hippocampus, where BNPI mRNA is expressed at high levels. No hybridizing signal for DNPI mRNA is observed in the glia-rich region of corpus callosum. In other regions examined, both mRNAs are moderately or highly expressed. These results indicate that BNPI and DNPI, which coordinate Na ϩ -dependent P i transport in the neuron-rich regions of the brain, may form a new class within the Na ϩ /P i cotransporter family. Key Words: cDNA cloning-Phosphate transport-Structurally related family-Neuron. J. Neurochem. 74, 2622Neurochem. 74, -2625Neurochem. 74, (2000.Inorganic phosphate (P i ) is essential for various cellular metabolic functions and signal transduction, and its homeostasis in the body is maintained primarily by the kidney (Murer and Biber, 1996). The cells in the proximal tubules of the kidney reabsorb P i in the glomerular filtrate through complex Na ϩ -dependent P i (Na ϩ /P i ) cotransport systems that are driven by the transmembrane electrochemical gradient for Na ϩ . Several cDNAs encoding distinct Na ϩ /P i cotransporters, which are classified into type 1 (NaP i -1-related), type 2 (NaP i -2-related), and type 3 (viral receptor-related) on the basis of molecular structure, have been identified in kidney and some other tissues (Murer and Biber, 1996;Werner et al., 1998). Amino acid comparison of the proteins shows weak overall homology (ϳ20% identity) between these types.A distinct type of the brain-specific Na ϩ /P i cotransporter (BNPI), which has ϳ30% amino acid identity to the type 1 proteins, has been described (Ni et al., 1994(Ni et al., , 1996. Northern blot analysis revealed that BNPI mRNA is expressed predominantly in brain, and in situ hybridization analysis revealed high levels of mRNA expression in certain neuron-rich regions of amygdala, cerebral cortex, and hippocampus. On the other hand, this mRNA was detected at low levels in substantia nigra, subthalamic nuclei, and thalamus, and no hybridization signals were detected in caudate nucleus and hypothalamus, suggesting that additional related proteins may be present in these regions to complement P i transport in brain.Rat pancreatic AR42J cells (Rosewicz et al., 1992) share the feature of pluripotency of the common precursor cells of the pancreas. Treatment of the cells with activin A converts them...