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Biomedical subjects

A Zeidler

Publications and source records attributed to A Zeidler.

At least 37 records · Page 2Linked to original sources
PubMed1989

Assessment of pancreatic islet-cell population in the hyperglycemic athymic nude mouse: immunohistochemical, ultrastructural, and hormonal studies.

Previous studies in diabetic animal models have demonstrated altered pancreatic islet-cell populations. To further characterize the diabetic syndrome in our athymic nude mouse colony, we studied the population of endocrine cells in pancreatic islets of 4-week-old normoglycemic and 8-week-old hyperglycemic athymic nude (nu/nu) mice using immunohistochemistry, morphometry, and electron microscopy. In normoglycemic 4-week athymic nu/nu mice, the proportions of B (insulin-secreting) cells and A (glucagon-secreting) cells were similar to those in control Balb/c mice; however, the D (somatostatin-secreting) cells were significantly decreased in nu/nu mice. The populations of B and A cells appeared to be normal in hyperglycemic 8-week-old nu/nu mice while there was a significant increase in the proportion of D cells when compared with the proportion in Balb/c mice. Electron microscopic studies indicated that the appearance of B and A cells was similar in the 8-week-old hyperglycemic nu/nu and in controls; however, the D cells appeared to be enlarged and were finely packed with electron-dense secretory granules. Radioimmunoassays of the pancreatic content (micrograms/g fresh pancreas) of insulin, glucagon, and somatostatin in pancreata in 8-week-old normal Balb/c and hyperglycemic athymic nude mice were similar; however, the somatostatin content was significantly increased in the 8-week-old hyperglycemic nu/nu mice compared with age and sex-matched controls. These results demonstrate an altered D cell population and an increase in somatostatin levels in the pancreatic islets of the hyperglycemic athymic nude mouse animal model.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Impaired exocrine pancreatic function in diabetics with diarrhea and peripheral neuropathy.

Exocrine pancreatic insufficiency has been observed in some diabetics with peripheral neuropathy and diarrhea. Several mechanisms may be responsible for this insufficiency: (1) pancreatic atrophy, (2) disruption of the cholinergic enteropancreatic reflexes, or (3) elevated serum levels of peptides such as glucagon and pancreatic polypeptide which are known to inhibit pancreatic exocrine secretion. To clarify the mechanism(s) involved in this exocrine pancreatic impairment, we studied 10 diabetics with diarrhea and peripheral neuropathy. Their results were compared to those of eight normal volunteers. Each subject underwent a standardized pancreatic function study which assessed nonstimulated secretion, the response to intrajejunal infusion of a mixture of amino acids, and the output following intravenous administration of secretin and cholecystokinin (CCK). In separate studies, the effect of a background infusion of bethanechol and secretin on the pancreatic response to CCK was assessed in six patients and six normal controls. Compared to normals, all diabetics exhibited a significant reduction in both enzyme and bicarbonate secretion to all stimuli. This reduction was not corrected by administering bethanechol. Plasma glucagon and pancreatic polypeptide levels in diabetics were not significantly higher than those in controls. We conclude that diabetics with diarrhea and peripheral neuropathy exhibit impairment of their exocrine pancreatic secretion and possible mechanisms for this are discussed.

Adult↗
PubMed1988

High prevalence of diabetes in young adult Ethiopian immigrants to Israel.

We performed oral glucose tolerance tests in 158 Ethiopian immigrants to Israel. The subjects were less than 30 yr of age, had lived in Israel less than or equal to 4 yr, and originated from villages in the Gondar and Ambovar regions of Ethiopia. Most had been subjected to famine conditions in Ethiopia and/or extreme hardship in Sudan before or during immigration. All were lean. They revealed a profound change in dietary habits since their arrival in Israel, with consumption of large amounts of refined carbohydrate in place of spicy stews and injura (Ethiopian pita) that had constituted dietary staples in better times in Ethiopia. According to National Diabetes Data Group criteria, 14 (8.9%) of the subjects had diabetes, and another 14 (8.9%) had impaired glucose tolerance. In addition, 13 subjects had a dramatic increase in capillary blood glucose levels (greater than 300 mg/dl) 1 h after ingestion of 75 g glucose, despite fasting and 2-h values well within the normal range, and they complained of associated symptoms during the 1st h of testing. Eleven of 137 men and 3 of 21 women had diabetes; 7 (5.1%) of the men and 7 (33%) of the women had impaired glucose tolerance. These results indicate a high prevalence of diabetes among young adult Ethiopian immigrants of relatively short residency in Israel, for which the factors responsible warrant further investigation.

Adolescent↗
PubMed1988

Abnormalities of the migrating motor complex in diabetics with autonomic neuropathy and diarrhea.

Diarrhea is a common symptom in long-standing diabetes. The pathogenesis of this diarrhea remains obscure, although it appears to be related to the development of autonomic neuropathy, which may cause several abnormalities including altered gut motility. We studied fasting gastrointestinal motility for a mean of 210 min in a group of 12 type-II diabetics with diarrhea. All patients had peripheral neuropathy and symptoms of autonomic neuropathy. Their motor activity was compared with that of a group of six normal volunteers. In addition, gastrointestinal transit time was assessed by the hydrogen breath test. The presence of bacterial overgrowth was assessed by the hydrogen breath test and culture of jejunal secretions. The diabetics showed grossly disordered motor activity. There was a complete absence of phase-III activity in two patients. Most phase III's commenced in the distal duodenum or jejunum. The phase-III component was often of short duration at each recording site. There was increased velocity of propagation between sites. Continuous phase-II activity was noted in some patients. Antral activity was absent or reduced during phase II. Gastrointestinal transit time was significantly prolonged in the diabetics. Bacterial overgrowth was demonstrated in three diabetic subjects. These motility abnormalities are nonspecific and are unlikely to play a major role in the pathogenesis of diabetic diarrhea.

Adult↗
PubMed1987

Avoidance responding in mice with diabetes mellitus.

In order to examine the behavioral concomitants of the neuroendocrine state of diabetes mellitus, the behavior of diabetic and normal male mice was compared in two behavioral paradigms. Diabetic mice were found to display significantly more passive avoidance to shock and significantly more submissive social behavior as compared to control mice. Furthermore, within the group of diabetic mice, mice showing the most passive avoidance also displayed the most submissive behavior. These findings suggest that diabetes mellitus may have effects on the neuroendocrine system that are manifested as changes in behavior.

Adrenocorticotropic Hormone↗
PubMed1987

Hyperglycemia and fight-flight behavior in nondiabetic and diabetic mice.

Glycemic responses to a resident-intruder encounter and to the drawing of blood from the retro-orbital sinus were studied in diabetic and normal male Swiss Webster mice. The diabetes induced with streptozotocin was either borderline, overt, or severe. The resident-intruder encounter consisted of a brief exposure to another male mouse trained to be aggressive. The blood collected was not sufficient (3% blood volume) to cause significant volume depletion. Behavior during the resident-intruder encounter was videotaped and later quantified. Borderline diabetic, overtly diabetic and nondiabetic mice responded to both procedures with significant increases in plasma glucose. The glycemic response to the resident-intruder encounter in these groups was significantly greater than that to the bleeding trial. The severely diabetic mice did not experience increases in plasma glucose in either test. Fight-flight behavior of nondiabetic mice was significantly correlated with increases in plasma glucose. Total activity was negatively correlated with change in plasma glucose in the borderline diabetic mice. In overtly diabetic mice no relationship between either measure and glucose increases was observed. These results indicate that plasma glucose elevation in overtly and severely diabetic mice is not as specific to behavior as in nondiabetic mice.

Aggression↗
PubMed1987

Reproductive defects in the male diabetic athymic nude mouse.

We have previously reported spontaneous hyperglycemia and impaired glucose tolerance in male athymic nude Balb/c mice. This colony also demonstrates impaired fertility. Previous studies in both athymic nude and diabetic obese (ob/ob) mice have shown reproductive abnormalities. It was the purpose of this investigation to further elucidate the endocrine abnormalities which might contribute to the reduced fertility observed in this model. Fasting plasma glucose was measured on each nude mouse to ensure that a diabetic state existed. Testes were removed and intratesticular testosterone and LH receptors were measured. Testosterone levels in diabetic, athymic nude Balb/c (DAN) mice were significantly decreased to 46.5% of control Balb/c mice. LH receptors in DAN mice were significantly elevated by 23.6% when compared to control animals. These results demonstrate that the impaired fertility observed in the DAN mouse may result from decreased testosterone production. The increased LH receptor levels seen in the DAN mouse might reflect a regulatory event in response to the decreased intratesticular testosterone levels.

Animals↗
PubMed1986

Agonistic behavior patterns in mice with streptozotocin-induced diabetes mellitus.

To examine the effects of the altered metabolic and hormonal state of diabetes mellitus on rodent social behavior, male Swiss Webster mice made diabetic with streptozotocin were tested in a resident-intruder encounter. Isolated diabetic and control mice were introduced as intruders into the home cages of aggression-trained resident mice. The encounters were videotaped and analyzed for frequencies and durations of agonistic behavior. Diabetic mice responded to the aggression of resident mice with significantly less investigation and aggression and significantly more static defense and escape behaviors than did control mice. Resident mice responded to less aggressive diabetic mice with more aggression and social investigation. Plasma corticosterone levels were significantly higher in diabetic mice compared to controls and positively correlated with submissive behavior in diabetic mice. These findings indicate that social behavior is altered in male diabetic mice and support the hypothesis that elevated pituitary-adrenal cortical activity and/or metabolic changes affect behavior in male diabetic mice.

Aggression↗
PubMed1984

Familial hyperinsulinemia due to a structurally abnormal insulin. Definition of an emerging new clinical syndrome.

We have identified a patient with mild diabetes, marked fasting hyperinsulinemia (89 to 130 microU of insulin per milliliter), and a reduced fasting C-peptide: insulin molar ratio of 1.11 to 1.50 (normal, greater than 4). The patient responded normally to exogenous insulin. However, her endogenous immunoreactive insulin showed reduced biologic activity during a glucose-clamp study with hyperglycemia and a reduced ability to bind to the insulin receptor and stimulate glucose transport in vitro. Family studies showed that five additional relatives in three generations had variable degrees of glucose intolerance, marked hyperinsulinemia, and a reduced peripheral C-peptide:insulin molar ratio. Restriction-endonuclease cleavage of DNA isolated from circulating leukocytes in the patient and in family members with hyperinsulinemia revealed loss of the MboII recognition site in one allele of the insulin gene--consistent with a point mutation at position 24 or 25 in the insulin B chain. Other studies using high-pressure liquid chromatography and detailed gene analysis have identified the defect as a serine for phenylalanine substitution at position 24 of the insulin B chain. The secretion of a structurally abnormal insulin should be considered in patients with hyperinsulinemia who respond normally to exogenous insulin and have a reduced C-peptide:insulin molar ratio. Glucose tolerance may range from relatively normal to overtly diabetic.

Adult↗
PubMed1984

Human insulin B24 (Phe----Ser). Secretion and metabolic clearance of the abnormal insulin in man and in a dog model.

We have already demonstrated that a hyperinsulinemic, diabetic subject secreted an abnormal insulin in which serine replaced phenylalanine B24 (Shoelson S., M. Fickova, M. Haneda, A. Nahum, G. Musso, E. T. Kaiser, A. H. Rubenstein, and H. Tager. 1983. Proc. Natl. Acad. Sci. USA. 80:7390-7394). High performance liquid chromatography analysis now shows that the circulating insulin in several other family members also consists of a mixture of the abnormal human insulin B24 (Phe----Ser) and normal human insulin in a ratio of approximately 9.5:1 during fasting. Although all affected subjects show fasting hyperinsulinemia, only the propositus and her father are overtly diabetic. Analysis of the serum insulin from two nondiabetic siblings revealed that normal insulin increased from approximately 2 to 15% of total serum insulin after the ingestion of glucose and that the proportion of the normal hormone plateaued or fell while the level of total insulin continued to rise. Animal studies involving the graded intraportal infusion of equimolar amounts of semisynthetic human [SerB24]-insulin and normal human insulin in pancreatectomized dogs (to simulate the secretion of insulin due to oral glucose in man) also showed both a rise in the fraction of normal insulin that reached the periphery and the attainment of a brief steady state in this fraction while total insulin levels continued to rise. Separate experiments documented a decreased hepatic extraction, a decreased metabolic clearance rate, and an increased plasma half-life of human [SerB24]-insulin within the same parameters as those determined for normal human insulin. These results form a basis for considering (a) the differential clearance of low activity abnormal insulins and normal insulin from the circulation in vivo, and (b) the causes of hyperinsulinemia in both diabetic and nondiabetic individuals who secrete abnormal human insulins.

Adult↗
PubMed1983

Immunoreactivity of human insulin of recombinant DNA origin.

To evaluate possible advantages of human insulin of recombinant DNA origin (HI) in the treatment of diabetic patients, we compared cellular and humoral immunoreactivities of HI and porcine insulin (PI). Anti-insulin IgE bound equal amounts of 125I-HI and 125I-PI. There was no difference between HI- and PI-stimulated lymphocyte transformation indices. The binding of 125I-HI with circulating anti-insulin IgG was lower compared with 125I-PI binding (12.1 +/- 1% versus 15.4 +/- 1.5%, P less than 0.001) in 60 insulin-treated cases. Thirteen sera were selected for high antibody titers and analyzed in detail. In the competitive inhibition assays, a 50% displacement of 125I-PI required a fourfold higher concentration of HI than PI. Although total insulin binding capacities were almost equal, 63 +/- 11 nM/L for PI and 60 +/- 12 nM/L for HI, the high-affinity antibodies had significantly reduced avidity for HI compared with PI. These differences in avidities suggest that HI may be useful in treatment of immune-type insulin resistance.

Adolescent↗
PubMed1982

Histocompatability antigens and immunoglobulin G insulin antibodies in Mexican-American insulin-dependent diabetic patients.

To determine the association of histocompatability antigens (HLA) with insulin-dependent diabetes (IDD) in Mexican-Americans, we determined HLA-A, -B, and -C specificities in 112 unrelated patients and 332 controls, and HLA-DR specificities in 85 patients and 209 controls. We also studied immunoglobulin G (IgG) insulin antibody formation in 56 Mexican-Americans with IDD, and the relationship between antibody formation and HLA-DR antigens. IDD patients have a significant increase in HLA-DR4 compared to the control population (chi 2 = 14.75; corrected P less than 0.0001). HLA-DR2 was not detected in any patient with IDD. A significant association between HLA-Aw30 and HLA-B18 was found in IDD patients (chi 2 = 9.39; P less than 0.05) as compared to controls. IgG insulin antibody formation was significantly increased in HLA-DR3- and -DR4-negative patients compared to that in patients positive for both antigens (P less than 0.05). These findings support previous observations in caucasians and black Americans indicating that HLA-DR specificities are associated with IDD and may play a role in determining its mode of inheritance, and perhaps its pathogenesis, independent of ethnic differences. HLA-DR immune-associated antigens are also of importance in determining IgG insulin antibody formation.

Adolescent↗
PubMed1982

Spontaneous hyperglycemia and impaired glucose tolerance in athymic nude BALB/c mice.

Basal plasma glucose, glucose tolerance, and insulin secretion were investigated in young and mature athymic nude BALB/c mice and in age-matched controls. Basal plasma glucose levels in male athymic nude mice were similar to those of controls at 1, 3, and 4 wk of age. At 6, 8, and 12 wk of age, male athymic nudes had significantly higher basal plasma glucose levels when compared with controls (P less than 0.01). Plasma immunoreactive insulin concentrations were similar in athymic nudes and controls at 1 wk of age, but at 3 wk of age and subsequently at 6, 8, and 12 wk athymic nude mice had significantly decreased insulin levels when compared with their age-matched controls (P less than 0.05). We found impaired glucose tolerance in male athymic nude mice at all age groups when compared with both female athymic nudes and control BALB/c mice. The discovery of a spontaneous diabetic syndrome (hyperglycemia, impaired glucose tolerance, and decreased insulin secretion) in a colony of athymic nude mice may provide an excellent model for studying the genetics and interactions between the immune and endocrine systems.

Animals↗
PubMed1981

Circadian variation in plasma prolactin, gonadotropins, and testosterone in diabetic male patients with and without impotence.

The circadian variation in plasma levels of prolactin, gonadotropins, testosterone, and glucose were studied in 10 young diabetic male patients. Four patients were asymptomatic without sexual dysfunction and six patients had organic impotence. The results of this study indicate that diurnal levels of luteinizing hormone, follicle-stimulating hormone, prolactin, and testosterone are similar in diabetic patients with and without impotence. During the nocturnal period, a sleep-related increase in plasma prolactin levels was noted in diabetic patients without impotence. In diabetic patients with impotence, plasma prolactin levels were similar during the diurnal and nocturnal periods. These results further support previous findings that diabetic patients with organic impotence do not have abnormal gonadotropin and testosterone levels.

Adult↗
PubMed1980

HLA-DRw antigens in Mexican-American and Black-American diabetic patients.

HLA-A, - B, and -C antigens were studied in 67 Mexican-American and 38 black-American diabetic patients who had the onset of their disease before age 31 yr. Control populations consisted of 322 Mexican-American and 367 black-American subjects for HLA-A, -B, and -C antigens. In addition, HLA-DRw antigens were studied in 60 Mexican-American and 34 black-American diabetic patients. Control populations for HLA-DRw antigens consisted of 189 Mexican-American and 145 black-American subjects. We found that juvenile-onset--diabetic patients of Mexican-American origin who had the onset of their disease before age 19 demonstrated a significant increase in HLA-DRw4. HLA-DRw4 was also significantly increased in black-American patients with juvenile-onset diabetes mellitus. HLA-DRw2 was not detected in any patient with juvenile-onset diabetes in either ethnic group. A significant association was found between HLA-B18 and HLA-DRw3 in Mexican-American juvenile-diabetic patients. These findings, which are comparable to those in similar Caucasian patients, provide additional information to support the hypothesis that HLA-DRw antigens play a major role in determining the susceptibility to juvenile-onset diabetes mellitus.

Adult↗
PubMed1979

Taste detection and preferences in diabetics and their relatives.

In order to determine whether a generalized defect in glucose recognition exists in diabetes, taste detection and preference were measured in adult onset diabetics (AOD), juvenile onset diabetics (JOD), and healthy first-degree relatives of diabetics (NR). Controls (C) were age and sex matched nondiabetics without first-degree diabetic relatives. The AOD and NR gorups showed significantly higher glucose thresholds than their controls. In contrast, glucose threshold in JOD was not different from C. The AOD group also demonstrated a higher sucrose threshold than C. This difference was not present for JOD or NR groups. No difference in salt detection was seen in any of the groups. Taste preference was assessed by two choice situations and ratings of test solutions of varying concentrations. No significant difference in glucose or sucrose preference were noted, but both the AOD and NR groups preferred lower salt concentrations than C. These findings indicate that thery may be a widespread impariment of cellular glucose recognition in AOD and their relatives, while JOD have a specific beta cell defect.

Adolescent↗