Altered regulation of insulin secretion by glucose is characteristic of individuals with type 2 diabetes mellitus, although the mechanisms that underlie this change remain unclear. We have now generated mice that lack the λ isoform of PKC in pancreatic β cells (βPKCλ–/– mice) and show that these animals manifest impaired glucose tolerance and hypoinsulinemia. Furthermore, insulin secretion in response to high concentrations of glucose was impaired, whereas the basal rate of insulin release was increased, in islets isolated from βPKCλ–/– mice. Neither the β cell mass nor the islet insulin content of βPKCλ–/– mice differed from that of control mice, however. The abundance of mRNAs for Glut2 and HNF3β was reduced in islets of βPKCλ–/– mice, and the expression of genes regulated by HNF3β was also affected (that of Sur1 and Kir6.2 genes was reduced, whereas that of hexokinase 1 and hexokinase 2 genes was increased). Normalization of HNF3β expression by infection of islets from βPKCλ–/– mice with an adenoviral vector significantly reversed the defect in glucose-stimulated insulin secretion. These results indicate that PKCλ plays a prominent role in regulation of glucose-induced insulin secretion by modulating the expression of genes important for β cell function.
Naoko Hashimoto, Yoshiaki Kido, Tohru Uchida, Tomokazu Matsuda, Kazuhisa Suzuki, Hiroshi Inoue, Michihiro Matsumoto, Wataru Ogawa, Sakan Maeda, Hiroaki Fujihara, Yoichi Ueta, Yasuo Uchiyama, Kazunori Akimoto, Shigeo Ohno, Tetsuo Noda, Masato Kasuga
Usage data is cumulative from September 2023 through September 2024.
Usage | JCI | PMC |
---|---|---|
Text version | 321 | 42 |
99 | 23 | |
Figure | 282 | 16 |
Citation downloads | 48 | 0 |
Totals | 750 | 81 |
Total Views | 831 |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.