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Biomedical subjects

H J Hahn

Publications and source records attributed to H J Hahn.

At least 127 records · Page 7Linked to original sources

[Immunoreactive insulin in the CNS of human fetuses and newborn infants of metabolically healthy and diabetic mothers--an immunohistochemical study].

The cellular localization and regional distribution of "insulin-like immunoreactivity" and "C-peptide immunoreactivity" were studied in brains of fetuses and newborns from normoglycaemic and diabetic mothers using immunohistochemical techniques. It is shown that "insulin-like material" and "C-peptide-like material" occur in the same nerve cells. No differences in regard to the localization of both polypeptides exist between abort material from normoglycaemic and diabetic mothers.

Brain Chemistry↗

Insulin- and glucagonlike peptides in the brain.

The cellular localization and regional distribution of insulin- and glucagonlike substance, C-peptide-like immunoreactivity, thiol:protein disulphide oxidoreductase, TPO (E.C.1.8.4.2.), and insulin/glucagon-specific proteinase, ISP (E.C.3.4.22.-), are studied in the CNS of man, adult and juvenile rats, mice, tortoises, and frogs by use of immunohistochemistry. Furthermore, the content of immunoreactive insulin, glucagon, and C-peptide was estimated in human cadaver brains by radioimmunoassay. It could be shown that insulinlike immunoreactive material is widely distributed in the human brain and the CNS of juvenile rats as well as in mice, whereas in the CNS of adult rats and nonmammalian animals (frogs, tortoises) the polypeptide is restricted to a few nerve cell populations. C-peptide immunoreactivity was demonstrated in human CNS in the same nerve cells as insulin. By use of two different glucagon-antisera it was revealed that gut-type glucagon occurs in many nerve cells of human and mouse brains, as well as in the CNS of juvenile rats. On the other hand, pancreas-type glucagon was less widely distributed in the human brain and nearly not detectable in the CNS of mice and rats. With the exception of neurosecretory nerve cells, there was a high degree of coincidence between the localization of insulin and TPO. The immunoreaction against the ISP antiserum was weak, but correlated well with the distribution of insulin-immunoreactivity. The occurrence of TPO and ISP in the brain demonstrates the ability of nervous tissue to degrade insulin and glucagon. By radioimmunoassay it was established that human brain contains insulin, glucagon and C-peptide at concentrations that exceed blood levels. We conclude from our data that, at least in part, cerebral insulin and glucagon are products of the brain itself.

Animals↗

Enhanced synthesis, storage, and secretion of insulin in pancreatic islets derived from obese subjects.

Insulin biosynthesis, content, and secretion were investigated in islets derived from pancreas specimens of normal weight (100.4 +/- 1.1% of ideal body weight) and obese (137.2 +/- 5.9% of ideal weight) patients. The pancreatic islets from the obese subjects were characterized by a significantly enhanced glucose-induced insulin secretion and biosynthesis and by an insulin content that was nearly double when compared with islets from the nonobese subjects. The results support the hypothesis that an enhanced beta-cell reactivity significantly contributes to the insulin hyperresponse observed in the obese state.

Adult↗

The glucagon/glucagon-like immunoreactivities in neurons of the human brain.

Using indirect immunofluorescence and Sternberger's PAP techniques on Bouin-fixed paraffin sections it was possible to show a glucagon/glucagon-like immunoreactivity in the following sites of the human brain: the Lamina V pyramidal cells of the Neocortex, the various neurons of the Hippocampus and Corpus amygdaloideum, the perikarya of neurons in the Nucleus ventromedialis and Nucleus infundibularis (arcuatus), the Nucleus ambiguus and the numerous granular cells of the cerebellar cortex. It was also possible with both techniques to find a similar distribution of the peptide hormones in the perikarya and the proximal parts of the neuronal extensions. Appropriate controls were used to confirm the results. Simultaneously, tissue specimens from the same brain regions were investigated for glucagon by radioimmunoassay. The glucagon content of nervous tissue was found to be much higher than the average glucagon concentration of blood plasma. The highest level of the polypeptide could be revealed for the Hypothalamus (up to 40 times higher than in blood plasma).

Brain Chemistry↗

Decrease of glucose-induced insulin secretion of pancreatic rat islets after irradiation in vitro.

Irradiation of pancreatic rat islets up to a dose of 2.5 Gy did neither alter glucose-nor IBMX-induced insulin secretion studied in vitro. The insulin as well as glucagon content of irradiated islets were similar as in the control tissue. This was also true in islets irradiated with 25 Gy which were characterized by a decreased insulin secretion in the presence of glucose and IBMX, respectively. Since we did not find indications of an enhanced hormone output in the radiation medium, we want to suggest that higher irradiation doses affect insulin release of pancreatic islets in vitro. This observation has to be taken into account for application of radioimmunosuppression for transplantation.

Animals↗

Protection of insulin secretion by magnesium during islet culture: independence of cAMP/or insulin accumulation.

Pancreatic rat islets cultured for 12 days maintained their insulin content and biosynthesis when cultivated at 10 mmol/l glucose. The glucose-induced insulin secretion investigated in a subsequent incubation period was, however, reduced. At a Mg++ concentration of 5.3 mmol/l in the tissue culture medium not only the content and biosynthesis, but also the secretory response of cultured islets remained fully preserved compared to freshly isolated islets. The secretory response of pancreatic islets cultured at 0.8 or 5.3 mmol/l Mg++ for 4 days was neither related to steady state concentrations of cAMP nor connected to the cAMP accumulation in response to IBMX. The results demonstrated that the favourable effect of Mg++ during a culture period on the subsequent insulin release is not directly related to hormone storage, synthesis and/or cAMP-accumulation.

1-Methyl-3-isobutylxanthine↗

The effect of irradiation on the development of low-dose streptozotocin diabetes in mice.

The effect of single-dose whole-body irradiation (6.0 Gy) on the development of low-dose streptozotocin diabetes in male C57 Bl/KsJ-mice was investigated. When irradiation precedes the SZ application the development of hyperglycemia could be prevented. Irradiation after SZ injections at the time of appearance hyperglycemia did not interfere with the onset of diabetes. The results underline the participation of radiosensitive immune cells as an etiologic factor of low-dose SZ diabetes.

Animals↗

[Fetal hyperinsulinism in early pregnancy--a cause of diabetic fetopathy?].

The influence of fetal hyperinsulinemia on the development of diabetic fetopathy was investigated. Human fetal pancreatic slices of fetus between the 12th and 26th weeks of pregnancy from non diabetic (n = 32) and diabetic (n = 18) women were incubated in vitro for one hour. The insulin secretion results clearly demonstrate an age dependent increase in both groups investigated, but the increase is much more pronounced in fetuses from diabetic women. The differences between the groups are present already during the 12th week of pregnancy. The results support the concept to normalize the metabolic control in pregnancy as early as possible in order to prevent the diabetic fetopathy.

Blood Glucose↗

Insulin and C-peptide in human brain neurons (insulin/C-peptide/brain peptides/immunohistochemistry/radioimmunoassay).

The regional distribution and cellular localization of insulin and C-peptide immunoreactivities were studied in human cadaver brains using the indirect immunofluorescence method, the peroxidase-antiperoxidase technique, and radioimmunoassay. Products of the immune reactions to both polypeptides were observed in most nerve cells in all areas of the brain examined. Immunostaining was mainly restricted to the cell soma and proximal dendrites. Radioimmunoassay revealed that human brain contains insulin and C-peptide in concentrations much higher than the blood, the highest being in the hypothalamus. These findings support the hypothesis that the "brain insulin" is--at least in part--produced in the CNS.

Aged↗

[Allogeneic transplantation of isolated islands of Langerhans into the liver of diabetic dogs with reference to its immunologic aspects].

By means of collagenase digestion and Ficoll gradient separation technique, viable islets of Langerhans were isolated from canine pancreases. These islets were transplanted into the liver of diabetic dogs. An experimental diabetes was induced by subtotal pancreatectomy and an application of 25 mg streptocotocin/kg bodyweight done twice. We performed the islet transplantation in several groups: 5 dogs differed from the donors by a strong histoincompatibility (EM-Test more than 15%). 5 dogs with a weak histoincompatibility and immunosuppression by Imuran and anti-thymocyte serum. The best results after transplantation were reached in the group with immunosuppression. There was an ameliorate effect on the hyperglycemia over a period of one year and we found significant differences in the glucose tolerance tests and in the immunoreactive insulin concentrations in contrast to the diabetic control dogs. No signs of portal hypertension and disturbance of the liver function were observed over the whole time of observations.

Animals↗

Insulin-like immunoreactivity in the human brain- A preliminary report.

The localization and regional distribution of insulin-like immunoreactivity (IRI) was studied in human brain autopsy material using the indirect immunofluorescence technique. A positive reaction for IRI could be observed in many neurons of the hypothalamus, the hippocampus, corpus amygdaloideum, medulla oblongata (especially within the nuclei of cranial nerves IX, X and XII), and the cerebral cortex, whereas the cerebellar cortex was lacking in immunohistochemically detectable insulin-like material. No nerve fibres containing polypeptides could be revealed. Additionally, the insulin content of various brain regions was estimated by radioimmunoassay. Insulin concentrations in human nervous tissue were found to be elevated in comparison to blood plasma levels.

Aged↗

C-peptide immunoreactive neurons in human brain.

C-peptide/C-peptide-like immunoreactivity was shown to be present in the cytoplasm of the soma and the proximal part of apical dendrites of some pyramidal cells in the Neocortex (Gyrus precentralis) and Hippocampus of man. C-peptide (connecting peptide) is a metabolic product in insulin biosynthesis and its localization in neurons is a proof for extrapancreatic insulin production.

Brain Chemistry↗

Effects of 3-isobutyl-1-methylxanthine on secretory response, cAMP accumulation and DNA synthesis of islets from postnatal and adult Wistar rats.

A possible role for cyclic adenosine-3'-5'-monophosphate (cAMP) in islet cell replication was examined in collagenase-isolated pancreatic islets from Wistar rats of different age and different metabolic state (non-pregnant, pregnant, days 15.5-17.5). Islets obtained from pregnant rats released significantly more insulin in response to 10 mmol/l glucose (culture for 24 h) and their DNA synthesis (incorporation of [3H]thymidine into islet DNA) was doubled compared to islets from non-pregnant controls. Islets obtained from 4-6 days old rats showed a maximal stimulation of DNA synthesis after exposure to 0.1 mmol/l IBMX (3-isobutyl-1-methylxanthine) whereas the cAMP accumulation and the insulin biosynthesis measured in a subsequent short-term incubation were dose-dependent stimulated up to 1.0 mmol/l IBMX. In islets of 12 days old rats or 3 months old rats, however, IBMX did not stimulate DNA synthesis or insulin release measured during culture, although the cAMP content per islet was significantly enhanced after culture in the presence of IBMX.

1-Methyl-3-isobutylxanthine↗

[Autogenous heterotopic pancreatic segment transplantation in dogs].

The own animal experimental investigations served the clearing of the most favourable variant of the operative technique in dog including organ perfusion and microsurgery. The middle-term endocrinic effects of a segmental transplant of nearly 35% of the pancreas from the dog were defined and the regulation of the endocrinic function of the denervated transplant was analysed. The morphological transformations in the transplant show new aspects by the exclusion of immunologic events. The evidence of the function of the transplant in vivo was led by the absolute lack of insulin after extirpating the transplant.

Animals↗