Unmyelinated fiber sensory neuropathy differs in type 1 and type 2 diabetes

Kawanishi, Hideki; Murakawa, Yûichi; Zhang, Weixian; Sima, Anders A. F.

doi:10.1002/dmrr.541

Cited by 71 publications

(95 citation statements)

References 57 publications

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“…Many reports demonstrated that CGRPergic nerves were highly dependent on neurotrophic support provided by insulin. 26,27 Based on these evidences, decrease in the density of CGRPergic nerve fibers in FDR mesenteric arteries might be involved in impaired insulin action on CGRPergic nerves, although further investigations are needed to test this mechanism. In contrast, previous reports demonstrate that sympathetic nerve terminals were less susceptible to insulin resistance than other organs in insulin-resistant model.…”

Section: Discussionmentioning

confidence: 99%

Hyperinsulinemia induces hypertension associated with neurogenic vascular dysfunction resulting from abnormal perivascular innervations in rat mesenteric resistance arteries

et al. 2011

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We previously reported that chronic hyperinsulinemia and insulin resistance induced by fructose-drinking loading elicited hypertension associated with abnormal neuronal regulation of vascular tone in an in vivo study using pithed rats. Therefore, to further clarify the detailed mechanisms of perivascular nervous system malfunction induced by chronic hyperinsulinemia, we investigated the neurogenic vascular responses and distribution of perivascular nerves using mesenteric vascular beds isolated from fructose-loaded rats with hyperinsulinemia. Male Wistar rats (6 weeks old) received 15% fructose solution as drinking fluid for 10 weeks (fructose-drinking rats, FDR), which resulted in significant increases in plasma levels of insulin, the glucose-insulin index, blood norepinephrine (NE) levels and systolic blood pressure, but not blood glucose levels, when compared with normal water-drinking rats (control rats). In perfused mesenteric vascular beds of FDR, enhanced adrenergic nerve-mediated vasoconstriction with no effect on NE-induced vasoconstriction and decreased calcitonin gene-related peptide (CGRP)-containing nerve-mediated vasodilation with no effect on CGRP-induced vasodilation were observed. Immunohistochemistry studies showed increased density of neuropeptide Y immunopositive adrenergic fibers and reduced density of CGRP immunopositive fibers in mesenteric arteries of FDR. Furthermore, FDR showed decreased CGRP content in dorsal root ganglia. These findings suggest that dysfunction of the neuronal vascular control system resulting from abnormal innervation of mesenteric perivascular nerves induced by the hyperinsulinemic state is responsible for the development of hypertension in FDR.

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Section: Discussionmentioning

confidence: 99%

Hyperinsulinemia induces hypertension associated with neurogenic vascular dysfunction resulting from abnormal perivascular innervations in rat mesenteric resistance arteries

et al. 2011

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“…Thermal plantar test. Latencies of hind paw withdrawal to thermal stimulation (42°C; 152 mW/cm 2 ) were used as measures of thermal hyperalgesia and were measured at 4 and 7 months using a UGO Biological Research apparatus (Comerio, Italy) (11,12). The time from heat source activation to the animal's self-withdrawal in seconds was measured six times in alternating hind paws.…”

Section: Methodsmentioning

confidence: 99%

“…Photographs were enlarged 10,000 times, scanned, and downloaded to a computerized image analysis system (Image-1; Universal Imaging, West Chester, PA). The following morphometric parameters of unmyelinated fibers were obtained: unmyelinated fiber number, fiber density (n/mm 2 ), mean fiber size (m 2 ), axon numbers per Schwann cell unit, and the frequencies of type 2 Schwann cell/axon relationship, collagen pockets, denervated Schwann cell profiles, and regenerating C-fibers (12). Identification and morphometry of substance P and calcitonin generelated peptide-positive DRG neurons.…”

Section: Methodsmentioning

confidence: 99%

“…Preweighed sciatic nerve segments were homogenized in lysis buffer (137 mmol/l NaC1, 20 mmol/l Tris HC1, pH 8.0, 1% NP40, 10% glycerol, 1 mmol/l phenylmethylsulfonyl fluoride, 10 g/ml aprotinin, 1 g/ml leupeptin, and 0.5 mmol/l sodium vanadate) and centrifuged (14,000 rpm for 20 min). The supernatants were loaded on MaxiSorp 96-well plates (Nalge Nunc International, Rochester, NY), and measurements were performed as previously described (12,13). Results were expressed as picograms per milligram protein in sciatic nerve and as picograms per ganglion in DRGs.…”

Section: Methodsmentioning

confidence: 99%

“…In previous studies, we have demonstrated a relationship between impaired insulin action and suppressed neurotrophic support, decreased expression of nociceptive neuropeptides, and degeneration of their parent dorsal root ganglion (DRG) cells (11)(12)(13).…”

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confidence: 99%

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C-Peptide Reverses Nociceptive Neuropathy in Type 1 Diabetes

et al. 2006

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We examined the therapeutic effects of C-peptide on established nociceptive neuropathy in type 1 diabetic BB/Wor rats. Nociceptive nerve function, unmyelinated sural nerve fiber and dorsal root ganglion (DRG) cell morphometry, nociceptive peptide content, and the expression of neurotrophic factors and their receptors were investigated. C-peptide was administered either as a continuous subcutaneous replacement dose via osmopumps or a replacement dose given once daily by subcutaneous injection. Diabetic rats were treated from 4 to 7 months of diabetes and were compared with control and untreated diabetic rats of 4-and 7-month duration. Osmopump delivery but not subcutaneous injection improved hyperalgesia and restored the diabetes-induced reduction of unmyelinated fiber number (P < 0.01) and mean axonal size (P < 0.05) in the sural nerve. High-affinity nerve growth factor (NGF) receptor (NGFR-TrkA) expression in DRGs was significantly reduced at 4 months (P < 0.01). Insulin receptor and IGF-I receptor (IGF-IR) expressions in DRGs and NGF content in sciatic nerve were significantly decreased in 7-month diabetic rats (P < 0.01, 0.05, and 0.005, respectively). Osmopump delivery prevented the decline of NGFR-TrkA, insulin receptor (P < 0.05), and IGF-IR (P < 0.005) expressions in DRGs and improved NGF content (P < 0.05) in sciatic nerve. However, subcutaneous injection had only marginal effects on morphometric and molecular changes in diabetic rats. We conclude that C-peptide exerts beneficial therapeutic effects on diabetic nociceptive neuropathy and that optimal effects require maintenance of physiological C-peptide concentrations for a major proportion of the day. Diabetes 55: [3581][3582][3583][3584][3585][3586][3587] 2006

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Current literature in diabetes

2006

Diabetes Metab. Res. Rev.

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Unmyelinated fiber sensory neuropathy differs in type 1 and type 2 diabetes

Abstract: The more severe molecular, functional and morphometric abnormalities of nociceptive C-fibers in type 1 insulinopenic rats compared to type 2 hyperinsulinemic rats suggest that impaired insulin action may play a more important pathogenetic role than hyperglycemia per se.

Cited by 71 publications

References 57 publications

Hyperinsulinemia induces hypertension associated with neurogenic vascular dysfunction resulting from abnormal perivascular innervations in rat mesenteric resistance arteries

Hyperinsulinemia induces hypertension associated with neurogenic vascular dysfunction resulting from abnormal perivascular innervations in rat mesenteric resistance arteries

C-Peptide Reverses Nociceptive Neuropathy in Type 1 Diabetes

Current literature in diabetes

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