Receptor for advanced glycation end products reveals a mechanism regulating thyroid hormone secretion through the SIRT1/Nrf2 pathway.

Advanced glycation end products (AGEs) play a causative role in the complications involved with diabetes mellitus (DM). Nowadays, DM with hypothyroidism (DM-hypothyroidism) is indicative of an ascended tendency in the combined morbidity. In this study, we examine the role of the receptor (RAGE) played for AGEs in thyroid hormone (TH) secretion via the silent information regulator 1 (SIRT1)/nuclear factor erythroid-derived factor 2-related factor 2 (Nrf2) pathway. Blood samples were collected from patients with type 2 DM (T2DM)-hypothyroidism and from patients with T2DM, followed by detection of serum AGEs level. The underlying regulatory mechanisms of RAGE were analyzed in association with the treatment of high glucose, siRNA against RAGE, AGE, SIRT1, or Nrf2 vector in normal immortalized thyroid Nthy-ori 3-1 cells. Serum of patients with T2DM-hypothyroidism indicated promoted levels of AGEs vs those with just T2DM. Both AGEs and high glucose triggered cellular damage, increased oxidative stress, as well as displayed a decreased survival rate along with TH secretion in the Nthy-ori 3-1 cells. Moreover, AGEs and high glucose also led to RAGE upregulation, both SIRT1 and NRF2 downregulation, and the decreased expression of TH secretion-related proteins in Nthy-ori 3-1 cells. Notably, these alternations induced by the AGEs can be reserved by silencing RAGE or upregulating either SIRT1 or Nrf2, indicating a mechanism of regulating TH secretion through the SIRT1/Nrf2 pathway. Collectively, our data proposed that AGEs and high glucose exerted a potent effect on cellular damage and TH deficiency in Nthy-ori 3-1 cells through the RAGE upregulation as well as SIRT1/Nrf2 pathway inactivation. This mechanism may underlie the occurrence of DM-hypothyroidism.

Association of a SLC30A8 genetic variant with monotherapy of repaglinide and rosiglitazone effect in newly diagnosed type 2 diabetes patients in China.

OBJECTIVE: To investigate a potential relationship between Solute carrier family 30 (zinc transporter) member 8 (SLC30A8) rs13266634 variant and efficacy of rosiglitazone or repaglinide in treating newly diagnosed Chinese type 2 diabetes patients. METHODS: A total of 209 diabetic patients without any antihyperglycemic history were recruited and treated with repaglinide or rosiglitazone randomly for 48 weeks (104 and 105 patients, respectively). Anthropometric measurements and clinical laboratory tests were carried out before and after the treatment. An non-synonymous variant rs13266634 was genotyped by matrix-assisted laser desorption ionization-time of flight mass spectroscopy. RESULTS: Ninety-one patients in repaglinide group and ninety-three patients in rosiglitazone group completed the study. Δ value of homeostasis model assessment of beta cell function (HOMA-B) and Δ value of fasting proinsulin levels were statistically significant between three genotype groups (P=0.0149 and 0.0246, respectively) after rosiglitazone treatment. However, no genotype association was observed in the repaglinide or rosiglitazone group with other parameters. CONCLUSION: The SLC30A8 variant was associated with the efficacy of insulin sensitizer monotherapy on insulin secretion in patients with newly diagnosed type 2 diabetes mellitus in Shanghai, China.

Madelung disease: A case report.

BACKGROUND: Madelung disease (MD) is a rare disorder of fat metabolism, resulting in diffuse, symmetrical and painless deposition of adipose tissue in subcutaneous superficial fascial space and/or deep fascia space of the head, neck and shoulders, etc. CASE SUMMARY: We report a case of MD accompanied by type 2 diabetes in a 61-year-old Chinese male. The patient presented with progressive fat deposition over the mandible, neck, abdomen and elbows. He had a history of smoking and alcohol abuse. Excessive fat deposition was seen in the mandible, elbows and the abdominal area of the patient by ultrasonic examination. Computed tomography showed diffuse and marked soft masses (fat density) in the subcutaneous superficial fascia space of the neck. The patient was diagnosed with MD. He was advised to abstain from alcohol and was followed up regularly. CONCLUSION: This report discusses the pathogenesis, diagnosis and treatment of MD, and raises the clinician's awareness of this disease.

A variation in NOS1AP gene is associated with repaglinide efficacy on insulin resistance in type 2 diabetes of Chinese.

AIM: To investigate a potential association between SNP rs10494366 in the neural nitric oxide synthase adaptor protein (NOS1AP) and efficacy of repaglinide (an insulin secretagogue) in newly diagnosed Shanghai Chinese type 2 diabetes patients. METHODS: A total of 104 newly diagnosed type 2 diabetes patients (69 men, 35 women) were recruited and treated with repaglinide for 24 weeks. Anthropometric measurements, clinical laboratory tests were obtained at baseline and after 24-week treatment. Genotyping was performed by sequencing. RESULTS: The baseline value of BMI, HOMA-IR, HOMA-B, and fasting insulin level were significantly different between GG, GT, and TT genotypes (P=0.024, 0.030, 0.005, and 0.007, respectively). Carriers of TT genotype were in significant insulin resistance at baseline. After 24-week repaglinide monotherapy, the Delta value of fasting insulin (P=0.019) and HOMA-IR (P=0.011) were significantly different. TT carriers had the least insulin resistance after treatment. The mixed model analysis showed that the variation had an interaction effect with repaglinide treatment only on HOMA-IR (P=0.013). CONCLUSION: A common variant in rs10494366 is associated with repaglinide monotherapy efficacy on insulin resistance in newly diagnosed Shanghai Chinese type 2 diabetes patients.