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H D Hartung

Publications and source records attributed to H D Hartung.

7 recordsLinked to original sources
PubMed1991

Diabetes mellitus-associated decrease in nerve growth factor levels is reversed by allogeneic pancreatic islet transplantation.

After an untreated 5-month duration of streptozotocin (STZ)-induced diabetes mellitus (DM), nerve growth factor (NGF) levels in BDE rats were decreased to 45-65% of control in the sympathetically innervated target organs iris and submandibular gland, in the superior cervical ganglion (containing NGF-dependent sympathetic perikarya projecting to the cranial targets), and in the NGF-transporting sciatic nerve. Successful allogeneic pancreatic islet transplantation (providing a physiological glucose homeostasis without immunosuppression) after 3-4 weeks of DM reversed the DM-related decrease in NGF levels 4 months after transplantation as compared with untreated diabetic rats. By contrast, NGF levels in the treated vas deferens (innervated by short postganglionic sympathetic neurons) remained increased as in the untreated diabetic rats (175% of control). Thus, DM-associated changes in endogenous NGF levels seem to be reversible by institution of metabolic control, at least at an early stage of DM when NGF-responsive neurons have not been deprived of NGF for a long time.

Animals↗
PubMed1990

Endogenous levels of nerve growth factor (NGF) are altered in experimental diabetes mellitus: a possible role for NGF in the pathogenesis of diabetic neuropathy.

Sympathetic and neural-crest derived sensory neurons consisting of unmyelinated and small myelinated fibers are known to be affected at an early stage in diabetes mellitus (DM). Since these peripheral neurons need nerve growth factor (NGF) for their development and maintenance of function in adulthood, changes in endogenous NGF levels could be of relevance for the pathogenesis of diabetic neuropathy (DNP). Using an improved two-site enzyme immunoassay for NGF, we have investigated whether endogenous NGF levels are altered in Sprague-Dawley rats with DM induced by a single injection of streptozotocin (STZ). STZ-treated rats are known to develop in many respects equivalents to neuropathic complications observed in human DM. We found in some sympathetically innervated target organs decreased NGF contents by maximally 56%: transiently in the iris 2 weeks and in the ventricle 12-24 weeks after DM induction and permanently in the submandibular gland already 3 days after DM induction. Several weeks after onset of DM, NGF content was increased by maximally 145-300% in most peripheral targets investigated, such as in iris, cardiac atrium and ventricle, spleen, prostate gland, and vas deferens. This is suggestive for an impaired NGF removal by NGF-sensitive neurons in diabetic rats. Moreover, NGF levels were decreased to minimally 42.6 +/- 4% of control in the NGF-transporting sciatic nerve. NGF levels began to decrease not before 3 weeks after DM induction and remained decreased with 54.0 +/- 5% of control even after 6 months duration of DM. About the same time (i.e., 2 weeks after induction of DM) NGF levels began to decrease in the superior cervical ganglion (where the sympathetic perikarya are located) to minimally 53.2 +/- 4% of control 12 weeks after DM induction. No altered NGF levels were observed during a 3-month duration of DM in the terminal ileum and sensory trigeminal ganglion. Since NGF exerts its neurotrophic action in the perikarya after its retrograde transport from the NGF-producing periphery, our results are consistent with the hypothesis that an alteration in NGF levels may play a role in the pathogenesis of DNP as far as sympathetic neurons are concerned. Thus, our results suggest that DM influences the production and/or transport of endogenous NGF and consequently, that a deprivation of this neurotrophic factor may account for some of the functional deficits known to occur in DNP, such as impaired catecholaminergic transmitter synthesis. This hypothesis possibly opens the way for new concepts in the therapy of DNP.

Animals↗