Requirement for the L-type Ca2+ channel α1D subunit in postnatal pancreatic β cell generation

The human L-type calcium channel Cav1.3 regulates insulin release and polymorphisms in CACNA1D associate with type 2 diabetes

“…However, a compensatory upregulation of Ca v 1.2 upon Cacna1d knockout, as detected by another group [8], could not be ruled out [39]. Studies in rats claimed Ca v 1.3 to be the major L-VGCC involved [12], which is similar to what is proposed for humans [15], although neither study quantified protein levels.…”

“…In the glutamate-releasing inner-ear hair cell, Ca v 1.3 has been shown to be responsible for the generation of spontaneous action potentials, important for the maturation of synaptic connections within the developing cochlea [44]. In a remarkable analogy, the postnatal maturation of mouse beta cells has also been suggested to be dependent on the presence of Ca v 1.3 [8], although spontaneous spiking during this process has never been investigated. Reflecting on our finding that a polymorphism in the gene encoding for Ca v 1.3 leads to decreased expression and reduced insulin release, our present data suggest Fisher's exact corrected p values are shown that this is not related to a decrease in islet mass or beta cell proportion.…”

“…Ca v 1.3, on the other hand, has been proposed to play a central role during murine postnatal beta cell generation and proliferation [8], but is also differentially regulated in a diabetogenic diet mouse model [9]. This isoform is characterised by a more negative activation threshold [10] and decreased calcium-channel blocker sensitivity [11] compared with Ca v 1.2, and has been suggested to be the main L-VGCC responsible for insulin release in rat beta cells [12,13].…”

Regulation of Gene Transcription by Voltage-gated L-type Calcium Channel, Cav1.3

“…The interfaces of the homogenize buffer 32, 32/40, and 40/50% are the plasma membrane fractions, whereas the vesicles and mitochondrial fraction are pelleted at the bottom of tube. Protein concentration was measured by the BCA method (Thermo Fisher Scientific, Rockford, IL) and analyzed by Western blot as described previously (17,18 1.3 Ϫ/Ϫ ) mice has previously been described (19). The null mutant mice were backcrossed onto the C57Bl/6J background for greater than 7 generations.…”

Efecto del tratamiento con leptina sobre la actividad del sistema glucosensor y la expresión de neuropéptidos implicados en la regulación de la ingesta de alimento en trucha arcoíris (Onchorhynchus mykiss)

“…En el cerebro de varios teleósteos se expresan los dos componentes del canal K ATP denominados SUR y Kir, con secuencias muy similares a las encontradas en mamíferos tales como Kir6.2 y SUR1, incluyendo Kir6-like y SUR-like en la trucha arco iris (Polakof et al, 2008c), Kir8 en el salmón del atlántico (Salmo salar) (Leong et al, 2008; número de acceso en GenBank: NM_001140360) y Kir6.3 y SUR1 en el pez zebra (Zhang et al, 2006). Por otra parte se han obtenido evidencias indirectas utilizando fármacos que avalan la existencia de canales K ATP en el cerebro de trucha arco iris (Polakof et al, 2007c).En los mamíferos, los genes que codifican los componentes del canal de calcio dependiente de potencial (VDCC) tipo L en las neuronas son Cav1.2 y Cav1.3 (Namkung et al, 2001). En los peces la presencia de este tipo de canal de calcio no ha sido estudiada completamente, y hasta la fecha, solamente se cuenta con la evidencia de que Cav1.2 y Cav1.3 se expresan en el cerebro del pez zebra (Sidi et al, 2004).…”