Effect of Experimental Diabetes on the Susceptibility of Myelin Proteins to Proteolysis

Abstract

To investigate abnormalities in peripheral nerve myelin in experimental diabetes, we studied the effects of the proteolytic enzymes trypsin and alpha-chymotrypsin on the proteins of this membrane, obtained from the sciatic nerves of normal rats and from animals made diabetic with streptozotocin. The dominant effect of the proteolytic enzymes was to incompletely degrade the major membrane protein (mol. wt. 28,000), with the appearance of new protein (mol. wt. 20,000). Using myelin isolated from the nerves of diabetic animals, the reaction was approximately one-half that of the controls (P less than 0.01) for both enzymes. When, however, the myelin protein affected by trypsin and chymotrypsin was isolated from the membrane and then incubated with the proteolytic enzyme, its proteolysis was complete and took place at the same rate in the diabetic animals and controls. These findings suggest that, in this model of experimental diabetes, there is an alteration in the structure of peripheral nerve myelin that inhibits interaction between the protein in the membrane bilayer and two water soluble proteolytic enzymes. This alteration could not be demonstrated in protein isolated from the membrane, suggesting that the change relates to the interaction of the protein and other components of myelin, rather than to chemical alteration in the protein per se.

The leptin receptor mutation of the obese Zucker rat causes sciatic nerve demyelination with a centripetal pattern defect

“…However, such 50-year-old etiology has been reconsidered and surveyed repeatedly 6,10,46,69,[75][76][77][78][79][80][81][82][83][84][85][86] but not necessarily with illustrations of the PNS-associated damages to demonstrate the myelinopathy progression. 6,79,87,88 Nowadays, specialists of diabetes can reappraise the old clinical neuropathy explanation 75 in NIDDM because the Zucker rats [40][41][42]89,90 , other animal studies 6,44,[46][47][48][49][50][51][52][53][87][88][89][90][91][92][93][94] , and several clinical cases 6,[54][55][56]…”

“…[1][2][3][4]7,9,87,[105][106][107][108][109][111][112][113]116 SCs and sciatic nerve changes Even though the dynamic mechanisms by which SC cytoplasm wraps constitute the enveloping major dense lines and the extracellular surface contacts form the minor lines of myelin can now be better understood than in the earliest investigations, the distribution and maintenance of many of the myelin components wrapped in associated sheaths are still unclear in the PNS [1][2][3][4][5][6]76,87,[117][118][119][120][121][122][123][124][125] ; this is especially true in the diabetes types. 76,[78][79][80][81][82]87,88,123,126,127 Recalling numerous investigations, some of them have clarified the single molecular marker's turnover during growth in vivo and in vitro. 3,…”

“…116,127,131 Many studies have emphasized the CNS defects 109,111,131,134 and reduced PNS disease's diagnostics into biopsy studies. [1][2][3][4][5][6]87,88 In PNS myelin, among all its non-phospholipid metabolome, large amounts of PGs or plasmalogens contribute to its architecture, integrity of adherence of the neuroplasm, and to nerve protection and insulation. [150][151][152][153][154] Further, the neuroplasm interacts with myelin both ways [155][156][157][158][159] , with cadherins [160][161][162][163][164][165][166] and others still to be found [165][166][167][168] as well as to place periaxin 169 with connexin 32 (Cx32).…”

“…The adipokine leptin is without receptors in obese Zucker rat The circulating adipokine leptin has been identified in wild and obese mice, and cloned. 35,88,[244][245][246][247] Then, leptin became important in clinics to understand biology of obesity and diabetes with a considerable bibliography. [248][249][250][251] Leptin receptors have been cloned and localized in rat CNS areas, including the lean and obese Zucker strains.…”

“…axis functions (endocrines, circadian rhythms, etc.). It is quite possible that, similarly in similar human cases, an equivalent defective receptor mutation, also localized in chromosome 7q, translates into faulty leptin receptor causing congenital obesity [54][55][56][57][58][59][60][61][62][63][64][65][66]88,244,246,[261][262][263][264] that can influence insulin activity. 38,[54][55][56][57][58][59][60][61][62][63][64][65][66]263,264 In these human cases, demyelination defects have yet to be found and studied.…”