Treatment-Induced Neuropathy in Diabetes (TIND)-Developing a Disease Model in Type 1 Diabetic Rats.

Treatment-induced neuropathy in diabetes (TIND) is defined by the occurrence of an acute neuropathy within 8 weeks of an abrupt decrease in glycated hemoglobin-A1c (HbA1c). The underlying pathogenic mechanisms are still incompletely understood with only one mouse model being explored to date. The aim of this study was to further explore the hypothesis that an abrupt insulin-induced fall in HbA1c may be the prime causal factor of developing TIND. BB/OKL (bio breeding/OKL, Ottawa Karlsburg Leipzig) diabetic rats were randomized in three groups, receiving insulin treatment by implanted subcutaneous osmotic insulin pumps for 3 months, as follows: Group one received 2 units per day; group two 1 unit per day: and group three 1 unit per day in the first month, followed by 2 units per day in the last two months. We serially examined blood glucose and HbA1c levels, motor- and sensory/mixed afferent conduction velocities (mNCV and csNCV) and peripheral nerve morphology, including intraepidermal nerve fiber density and numbers of Iba-1 (ionized calcium binding adaptor molecule 1) positive macrophages in the sciatic nerve. Only in BB/OKL rats of group three, with a rapid decrease in HbA1c of more than 2%, did we find a significant decrease in mNCV in sciatic nerves (81% of initial values) after three months of treatment as compared to those group three rats with a less marked decrease in HbA1c <2% (mNCV 106% of initial values, p ≤ 0.01). A similar trend was observed for sensory/mixed afferent nerve conduction velocities: csNCV were reduced in BB/OKL rats with a rapid decrease in HbA1c >2% (csNCV 90% of initial values), compared to those rats with a mild decrease <2% (csNCV 112% of initial values, p ≤ 0.01). Moreover, BB/OKL rats of group three with a decrease in HbA1c >2% showed significantly greater infiltration of macrophages by about 50% (p ≤ 0.01) and a decreased amount of calcitonin gene related peptide (CGRP) positive nerve fibers as compared to the animals with a milder decrease in HbA1c. We conclude that a mild acute neuropathy with inflammatory components was induced in BB/OKL rats as a consequence of an abrupt decrease in HbA1c caused by high-dose insulin treatment. This experimentally induced neuropathy shares some features with TIND in humans and may be further explored in studies into the pathogenesis and treatment of TIND.

The Role of Iron and Nerve Inflammation in Diabetes Mellitus Type 2-Induced Peripheral Neuropathy.

Peripheral diabetic neuropathy (PDN) is one of the most common complications of diabetes mellitus. Previous studies showed an association between dietary iron load and inflammation in the development of PDN in a rat model of type 1 diabetes (T1D). Here we investigated the role of iron and neural inflammation in development of PDN in a animal model of obesity and type 2 diabetes (T2D). 3-month-old db/db mice were fed with a high, standard or low iron diet for 4 months. High iron chow lead to a significant increase in motor nerve conduction velocities compared to mice on standard and low iron chow. Direct beneficiary effects on lowering blood glucose and HbA1c concentrations were shown in the high iron treated diabetic mice. Numbers of pro-inflammatory M1 macrophages were reduced in nerve sections, and anti-inflammatory M2 macrophages were increased in db/db mice on high iron diet compared to other groups. These results confirm and extend our previous findings in STZ-diabetic rats by showing that dietary non-hem iron supplementation may partly prevent the development of PDN in opposition to iron restriction. The identification of these dietary iron effects on the metabolic and inflammatory mechanisms of PDN supports a role of dietary iron and leads us to suggest testing for iron levels in human diabetic patients.

Effect of Thermal Processing on Antioxidant Activity and Cytotoxicity of Waste Potato Juice.

Potato juice (PJ), commonly considered a burdensome waste, is rich in various compounds with bioactive properties. It has long been considered a remedy for gastric problems in traditional folk medicine. If valorization of PJ through implementation in the production of functional foods is to be considered, stabilization methods must be developed to allow long-term storage of this seasonal product. It is important that such methods are chosen with regard to their effect on the bioactive value of the obtained product. In this study, the impact of four stabilization methods on the antioxidant and cytotoxic activities of PJ was investigated. Elevated temperatures were used in thermal deproteinization used to obtain DPJW (deproteinated potato juice water) and spray-drying of FPJ (fresh potato juice) that resulted in SDPJ. Freeze drying and cryoconcentration were the low temperature processing methods that yielded PJL (potato juice lyophilisate) and CPJ (cryocorncentrated potato juice), respectively. All processed materials were characterized chemically and compared with raw materials in terms of phenolic compounds content, antioxidant activity as well as cytotoxicity to human tumor cells isolated from the gastric mucosa (Hs476T cell line), colon (Caco-2 and HT-29 cell lines), and normal cells isolated from the small intestine and colon epithelium (IEC-6 and NCM460 cell lines). It was stated that high-temperature processes - thermal deproteinization and spray-drying - yielded products with increased antioxidant potential (TEAC) that also showed increased cytotoxic activity towards intestinal cancer cells. At the same time the cytotoxicity towards normal cells remained on par with that of fresh PJ (IEC-6 cells) or decreased (NCM460 cells). Thermal deproteinization significantly decreased the content of glycoalcaloids in the juice, while spray drying did not have such an effect. The two low-temperature processes investigated - cryoconcentration and freeze drying - did not affect the PJ cytotoxic activity towards any of the cell lines used in the tests, whereas they did affect the antioxidant properties and glycoalcaloids content of PJ.