The role of calcium/calmodulin-dependent protein kinase cascade in glucose upregulation of insulin gene expression.

A number of factors have been reported to affect insulin synthesis in beta-cells. Although glucose is the most important regulator of insulin gene expression in pancreatic beta-cells, the mechanisms whereby glucose stimulates insulin gene transcription in response to changes in glucose concentration have not been clarified yet. In this study, we examined the role of the Ca(2+)/calmodulin (CaM)-dependent protein kinase (CaM-K) cascade in transcriptional activation of insulin. RT-PCR, Western blotting, and immunohistochemical staining analysis revealed that CaM-K kinase-alpha (CaM-KKalpha) and CaM-KIV were localized in rat pancreatic beta-cells and their cell line, INS-1. Exposure of INS-1 cells to 11.2 mmol/l glucose elicited an increase of insulin promoter activity as well as upregulation of CaM-KIV activity within 2 min after stimulation. We investigated the influence on insulin promoter activity of the constitutively active form (CaM-KIVc) or dominant-negative mutant (CaM-KIVdn) of CaM-KIV in transfected INS-1 cells. CaM-KIVc alone was sufficient, and the upstream kinase, CaM-KK, was enhanced to upregulate the insulin promoter activity in INS-1 cells. Furthermore, cotransfection of CaM-KIVdn suppressed to a significant degree the glucose-upregulated activity of the insulin promoter. Taken together, these results indicated that the CaM-KK/CaM-KIV cascade might play an important role in glucose-upregulated transcriptional activation of the insulin gene.

[Evaluation of postoperative pain relief after video-assisted thoracoscopic surgery (VATS) for spontaneous pneumothorax].

BACKGROUND: We have investigated correlation between postoperative pain and chest tube insertion after video-assisted thoracoscopic surgery (VATS) for patients with spontaneous pneumothorax, and have evaluated preemptive analgesia by intercostal nerve block (ICB) using bupivacaine. METHODS: Thirty patients received VATS for spontaneous hemi-pneumothorax. There were two groups of the patients; Group CT received chest tube before the operation, and the Group NCT received no chest tube. Both groups received general anesthesia combined with ICB by 0.25% bupivacaine at the surgical region before operation. Postoperative pain was assessed using visual analogue scale (VAS scale: 0-10) and the need for additional supplemental analgesics before the operation, and at 6 and 24 hours after the operation, and at 3, 7, 14, and 30 days after the operation. RESULTS: Visual analogue scale in Group NCT before the operation, and at 24 hours, 3, 7, 14, and 30 days after the operation was significantly lower than that of Group CT. Analgesic requirements were significantly lower in the Group NCT than in the Group CT. CONCLUSIONS: We should avoid the insertion of a chest tube before the operation as much as possible. Furthermore early operation and intercostal nerve blockade before the operation were useful to prevent postoperative pain and its shift to chronic post thoracostomy pain.

A case of Dunnigan-type familial partial lipodystrophy (FPLD) due to lamin A/C (LMNA) mutations complicated by end-stage renal disease.

Dunnigan-type familial partial lipodystrophy (FPLD) is a rare monogenic adipose tissue disorder in which the affected subjects have increased predisposition to insulin resistance and related metabolic complications, such as glucose intolerance, diabetes, dyslipidemia, and hepatic steatosis. Our patient was a 35-year-old female who had been receiving insulin injection therapy for diabetes mellitus and was transferred to our hospital. She was diagnosed with FPLD on the basis of the following symptoms: increase in subcutaneous fat in the face, neck, and upper trunk; loss of subcutaneous fat in the lower limbs and the gluteal region. We found a heterozygous CGG to CAG transition in codon 482 of exon 8 in the gene encoding lamin A/C (LMNA), which leads to an arginine to glutamine substitution (R482Q). At the time of admission, her serum creatinine level was 8.4 mg/dl, and her blood urea nitrogen (BUN) level was 81 mg/dl. Her serum creatinine level was elevated and hemodialysis was performed twice every week. However, she died of cerebral hemorrhage 9 months after hemodialysis. Although it is uncommon for patients with FPLD to exhibit renal dysfunction and require hemodialysis, this case suggests the need for careful analysis of renal function in a patient with FPLD.