A curcumin derivative J147 ameliorates diabetic peripheral neuropathy in streptozotocin (STZ)-induced DPN rat models through negative regulation AMPK on TRPA1

Abstract Purpose: To investigate the specific molecular mechanisms and effects of curcumin derivative J147 on diabetic peripheral neuropathy (DPN). Methods: We constructed streptozotocin (STZ)-induced DPN rat models to detected mechanical withdrawal threshold (MWT) in vivo using Von Frey filaments. In vitro, we measured cell viability and apoptosis, adenosine 5'-monophosphate-activated protein kinase (AMPK) and transient receptor potential A1 (TRPA1) expression using MTT, flow cytometry, qRT-PCR and western blot. Then, TRPA1 expression level and calcium reaction level were assessed in agonist AICAR treated RSC96cells. Results: The results showed that J147reduced MWT in vivo, increased the mRNA and protein level of AMPK, reduced TRPA1 expression and calcium reaction level in AITCR treated RSC96 cells, and had no obvious effect on cell viability and apoptosis. Besides, AMPK negative regulated TRPA1 expression in RSC96 cells. Conclusions: J147 could ameliorate DPN via negative regulation AMPK on TRPA1 in vivo and in vitro. A curcumin derivative J147might be a new therapeutic potential for the treatment of DPN.

The Role of Insulin Resistance in Diabetic Neuropathy in Koreans with Type 2 Diabetes Mellitus: A 6-Year Follow-Up Study

PURPOSE: We previously reported that insulin resistance, low high-density lipoprotein (HDL) cholesterol, and glycaemic exposure Index are independently associated with peripheral neuropathy in Korean patients with type 2 diabetes mellitus. We followed the patients who participated in that study in 2006 for another 6 years to determine the relationship between insulin resistance and neuropathy. MATERIALS AND METHODS: This study involved 48 of the original 86 Korean patients with type 2 diabetes mellitus who were referred to the Neurology clinic for the assessment of diabetic neuropathy from January 2006 to December 2006. These 48 patients received management for glycaemic control and prevention of diabetic complications in the outpatient clinic up to 2012. We reviewed blood test results and the nerve conduction study findings of these patients, taken over a 6-year period. RESULTS: Low HDL cholesterol and high triglycerides significantly influenced the development of diabetic neuropathy. Kitt value (1/insulin resistance) in the previous study affected the occurrence of neuropathy, despite adequate glycaemic control with HbA1c <7%. Insulin resistance affected the development of diabetic neuropathy after 6 years: insulin resistance in 2006 showed a positive correlation with a change in sural sensory nerve action potential in 2012. CONCLUSION: Diabetic neuropathy can be affected by previous insulin resistance despite regular glycaemic control. Dyslipidaemia should be controlled in patients who show high insulin resistance because HDL cholesterol and triglycerides are strongly correlated with later development of diabetic neuropathy.

Tratamiento de la neuropatía diabética / Diabetic neuropathic treatment

La polineuropatía diabética es una complicación progresiva que afecta a la mayoría de los pacientes con diabetes mellitus de larga duración, y que es capaz de deteriorar gravemente su calidad de vida. En los últimos años se han desarrollado medidas terapéuticas que permiten mejorar los síntomas y la función nerviosa, y en algunos casos, prevenir y detener el daño neuronal, e incluso, favorecer la regeneración de las fibras nerviosas. La utilidad de estos tratamientos se apoya en investigaciones realizadas en animales y en seres humanos como son: a) control estricto de la glucemia (insulina), b) inhibición de la aldosa reductasa (tolrestato), c) prevención de la glucación de proteínas canino-guanidina), d) disminución de la isquemia nerviosa (vasodilatadores, ácido gamalinolénico), y e) administración de factores neurotróficos (gangliosidos). El más investigado y con evidencias más sólidas de su utilidad es el control de la glucemia. Se sugiere que el tratamiento se inicie tempranamente, pues en la neuropatía avanzada hay una severa pérdida de fibras nerviosas que dificulta la recuperación

Neuropatía diabética: sensibilidad térmica y control metabólico en diabéticos no insulinodependientes / Diabetic neuropathy: thermal sensation and metabolic control in non insulin dependent diabetics

Background: The early detection of peripheral neuropathy in diabetics is important since it is the main riskfactor for lower limb trophic lesions in diabetics. Aim: To assess the relationship between feet thermal sensation threshold and metabolic control in ambulatory non-insulin-dependent diabetics. Pattients and methods: A random sample of 34 non-insulin-dependent diabetic followed for more than five years in a special clinic, out of 368 patients, was selected. Warmth sensation thresbolds were measured in the dorsum of booth feet using a MSTP-III thermostimulator The average value of all glycosylated hemoglobins obtained during the 9.7 ñ 5.3 years of follow up for each patient was calculated. A multiple stepwise regression analysis was performed between thermal sensation as the dependent variable and glycosylated hemoglobin, fasting blood glucose, age and diabetes duration. Results: The regression model disclosed glycosylated hemoglobin as the only independent predictor of warmth sensation threshold (partial r= 0.385; p= 0.043). Fifteen diabetic patients with metabolic control, defined as those with a mean glycosylated hemoglobin of less than 9.5 percent, had a warmth sensation threhold of 35.6 ñ 3.7 ºC, whereas 19 diabetics with a bad control (glycosylated hemoglobin 9.5 percent) had a threshold of 39 ñ 3.8 ºC(p= 0.017). Conclusions: In this group of diabetics there is a relationship between the severity of distal polyneuropathy and the metabolic contrl, assessed with glycosylated hemoglobin levels

Clinical and metabolic study of diabetic neuropathy

The present study included 150 patients with non insulin dependent diabetes mellitus. They were 111 males and 39 females, aged from 31-66 with a mean age of 50 +/- 7.4 years. The duration of diabetes mellitus ranged from 3-25 years with a mean duration of 8.6 +/- 3.9 years. Clinical results showed that 67 cases of the 150 diabetic patients [44.7 percent] had symptomatic peripheral neuropathy. Out of them, 21 [14 percent] cases had subjective symptoms of neuropathy without objective signs and 46 cases [30.7 percent] showed symptoms and signs of diabetic polyneuropathy. Diabetic autonomic neuropathy was detected in 24 [16 percent] patients; all of them had objective neuropathy. Also diabetic cranial neuropathy was present in 2 [1.3 percent] subjects. There were positive correlations between duration of diabetes and severity of hyperglycemia as well as clinical severity; while age had statistically non significant correlation with both