Possible contribution of taurine to distorted glucagon secretion in intra-islet insulin deficiency: a metabolome analysis using a novel α-cell model of insulin-deficient diabetes.

Glycemic instability is a serious problem in patients with insulin-deficient diabetes, and it may be due in part to abnormal endogenous glucagon secretion. However, the intracellular metabolic mechanism(s) involved in the aberrant glucagon response under the condition of insulin deficiency has not yet been elucidated. To investigate the metabolic traits that underlie the distortion of glucagon secretion under insulin deficient conditions, we generated an αTC1-6 cell line with stable knockdown of the insulin receptor (IRKD), i.e., an in vitro α-cell model for insulin-deficient diabetes, which exhibits an abnormal glucagon response to glucose. A comprehensive metabolomic analysis of the IRKD αTC1-6 cells (IRKD cells) revealed some candidate metabolites whose levels differed markedly compared to those in control αTC1-6 cells, but also which could affect the glucagon release in IRKD cells. Of these candidates, taurine was remarkably increased in the IRKD cells and was identified as a stimulator of glucagon in αTC1-6 cells. Taurine also paradoxically exaggerated the glucagon secretion at a high glucose concentration in IRKD cells and islets with IRKD. These results indicate that the metabolic alterations induced by IRKD in α-cells, especially the increase of taurine, may lead to the distorted glucagon response in IRKD cells, suggesting the importance of taurine in the paradoxical glucagon response and the resultant glucose instability in insulin-deficient diabetes.

The cytokeratin-18 fragment level as a biomarker of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus.

BACKGROUND: The serum cytokeratin-18 fragment (CK-18) concentration has been suggested to be a biomarker of nonalcoholic fatty liver disease (NAFLD), although its usefulness in patients with type 2 diabetes mellitus (T2DM) is unknown. METHODS: The study was divided into two parts. In the first cross-sectional study, a total of 200 patients with T2DM and 58 healthy control subjects were recruited. NAFLD was diagnosed using ultrasonography. In the subsequent longitudinal study, we evaluated the three-month change (Δ) in the CK-18 concentration and other parameters in 40 T2DM patients with NAFLD. RESULTS: The serum CK-18 values were significantly higher in the NAFLD group than in the nonNAFLD group among both diabetic and nondiabetic subjects. The CK-18 concentration was found to be an independent determinant of NAFLD and was positively correlated with the ultrasonography score and AST and ALT concentrations in the T2DM patients. Positive correlations were also identified between the CK-18 and transaminase concentrations in the T2DM and NAFLD cohorts. ΔCK-18 was found to be significantly associated with ΔBMI in the T2DM patients with NAFLD. CONCLUSIONS: A dose effect between the CK-18 concentration and the severity of NAFLD was found in the T2DM patients; thus, the CK-18 concentration is a potentially useful biomarker for assessing the efficacy of treatment and the improvement in NAFLD in patients with T2DM.

Glycaemic instability correlates with a hyperglucagonaemic response in patients with type 1 diabetes without residual beta-cell function.

We investigated the association between arginine-stimulated glucagon secretion (AUCIRG) and several parameters of glycaemic variability in 12 patients with type 1 diabetes without residual beta-cell function. AUCIRG positively correlated with the SD and mean amplitude of glycaemic excursions, thus glucagon might contribute to glycaemic instability, independent of endogenous insulin.

[Case of incomplete brown-Séquard syndrome after thoracic herpes zoster infection].

e report an 87-year-old woman who presented with incomplete Brown-Séquard syndrome after reactivation of varicella-zoster virus (VZV). Two days after herpes zoster in the right side of the chest, she developed weakness of the right lower limb. Neurological examination revealed a spastic palsy in the right lower limb and left side loss of pain and temperature sense to T6. However, vibration and position sense was not impaired in both sides. Spinal T2-weighted MR images showed a high-intensity lesion in the right side of the spinal cord except posL terior funiculus at the level of T2. Cerebrospinal fluid analysis showed 109 leukocytes/mm3, 79 mg/dl protein, negative VZV PCR, elevated titer of anti-VZV IgM and IgG, and increase of IgG index. Although she was treated with a combination of acyclovir and steroid pulse therapy, her weakness in the right lower limb was not improved. In this case, since the posterior funiculus circulated from the posterior spinal artery was not involved, the incomplete Brown-S6quard syndrome may be caused by spinal cord infarction due to VZV vasculitis of the anterior spinal artery.