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H C Fehmann

Publications and source records attributed to H C Fehmann.

At least 19 recordsLinked to original sources
PubMed2003

[A 47-year-old man with "pure autonomic failure" and pernicious anemia].

HISTORY AND CLINICAL FINDINGS: A 47-year-old man with a known and substituted vitamin B12 deficiency presented with increasing symptoms associated with orthostatic hypotension, neck pain and micturitional and visual disturbances. CLINICAL AND LABORATORY TESTS: Catecholamines were strongly reduced in plasma and urine. DIAGNOSIS, TREATMENT AND CLINICAL COURSE: A pure autonomic failure was diagnosed and therapy with fludrocortisone, yohimbine and erythropoetine was started. Symptoms with the exception of micturitional disturbances improved strongly. CONCLUSIONS: Multiple-drug treatment of pure autonomic failure is successful. The prognosis is good.

Adrenergic alpha-Antagonists↗
PubMed2001

[The alpha-glucosidase inhibitor miglitol for the treatment of type 2 diabetes mellitus in the doctor's office].

BACKGROUND AND METHOD: An observational study was carried out according to and 67 (6) AMG from october 1999 until august 2000. 2654 patients with diabetes mellitus type 2 were treated by 766 physicians for 3 months with alpha-glucosidase inhibitor miglitol. The aim of the study "DiaLife" was to obtain data regarding the effectiveness and safety of miglitol in the daily practice. Pre- and postprandial glucose levels, HbA1c, triglycerides, urin glucose, microalbuminuria and body weight were used as parameters of effectiveness. Also an increasing treatment scheme was used. Side effects were documented by the care providing physicians and evaluated by the global tolerability analysis. RESULTS: Males and females showed a balanced distribution. The average age was 62 years and the average duration of diabetes was 5 years. Concomitant diseases were described for 82% of patients: 62% of patients suffered from hypertension, 43% from hyperlipidemia and 22% from coronary heart disease. 64% of patients were already on treatment for diabetes. The mostly prescribed drugs were sulfonylureas and biguanides. Miglitol was gradually increased (first week 1 x 50 mg daily, second week 2 x 50 mg daily, until the third week 3 x 50 mg daily) and the final dosages were 3 x 50 mg or 3 x 100 mg miglitol daily. HbA1c, pre- and postprandial glucose levels were strongly reduced. The HbA1c decreased from 8.4% to 7,1%. Pre- and postprandial glucose levels were reduced minus 46 mg/dl and minus 59 mg/dl. The average decrease of body weight was 1,9 kg; the effect was augmented in individuals with higher BMI. Adverse effects were reported in 47 patients and occured mainly in the GI tract. There were no problems in the combination of miglitol with other pharmacological substance groups. CONCLUSION: The alpha-glucosidase inhibitor miglitol is an efficient and safe drug for the treatment of diabetes mellitus type 2. It is an ideal tool for mono- and combination therapy. It reduces remarkably the body weight. 90% of physicians judged miglitol's efficiency and safety as "very good" or "good".

1-Deoxynojirimycin↗
PubMed2001

Effects of the nitric oxide/cGMP system compared with the cAMP system on airway mucus secretion in the rat.

Mucus secretion of the airways is under the control of a variety of intracellular second messenger systems. Cyclic nucleotides such as cGMP, coupled to the recently discovered nitric oxide system, and cAMP are of outstanding interest in this respect. The present study used the modified Ussing chamber technique and mucins labelled with (35)SO(4) to investigate mucus secretion in the rat trachea to clarify the contribution of these different second messenger systems to the control of mucin secretion.A variety of drugs affecting either the generation or the breakdown of the respective cyclic nucleotides were used. Neither drugs interfering with nitric oxide synthase nor the phosphodiesterase isoenzyme responsible for cGMP breakdown nor cGMP analogues were able to affect mucus secretion. In contrast, stimulation of adenylate cyclase or inhibition of the respective phosphodiesterase resulted in a potent increase of mucus secretion. In conclusion, we failed to show the involvement of the nitric oxide/cGMP system, whereas the cAMP system seems to be a very efficient regulator of mucus secretion in the rat trachea.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed2000

[Treatment of type 2 diabetes mellitus with the alpha-glucosidase inhibitor Miglitol in the doctor's office].

BACKGROUND AND METHOD: In an observational study carried out in accordance with paragraph 67 (6) of the AMG and beginning in May 1998, 846 patients with type 2 diabetes mellitus were followed for a period of three months by general practitioners and internists. The aim was to acquire data on the efficacy and tolerability of the alpha-glucosidase inhibitor, Miglitol, used in the doctor's office setting. A major point of interest was to determine the feasibility of using a regimen of gradually increasing doses in daily practice. The parameters investigated were HbA1c, fasting blood glucose and changes in the patient's weight. Any side effects were recorded by the care-providing physician and evaluated in the global tolerability analysis. RESULTS: The demographic data showed a balanced distribution of male and female patients. The average age of the men was 62 years, of the women 65 years. At the start of the observation, 62% of the patients had polyneuropathy, 35% retinopathy, and 25% nephropathy. 620 patients (73.3%) had received prior antidiabetic treatment. Depending on tolerability, the dose of Miglitol was increased individually from an initial 3 x 50 mg to 3 x 100 mg. 63.8% of the patients remained at the initial dose of 3 x 50 mg. A clear decrease in both HbA1c and fasting blood glucose was observed under treatment. During the course of the three months, the BMI decreased slightly by an average of 0.4 kg/m2, a desirable side effect in this patient group. Adverse reactions occurred in 39 ofthe 846 patients in the form of flatulence, diarrhea and enterospasm. CONCLUSION: Treatment with the alpha-glucosidase inhibitor Miglitol proved to be highly effective and readily combinable with other antidiabetics. Its efficacy was assessed to be "very good" or "good" by 86.5% of the physicians, and more than 90% assessed its tolerability to be "very good" or "good".

1-Deoxynojirimycin↗
PubMed2000

Treatment of endocrine gastroenteropancreatic tumors with somatostatin analogues.

Somatostatin is a hormone that regulates the function of several exocrine and endocrine glands. The peptide mediates its actions via five different receptors. These proteins are expressed in a tissue-specific manner. Somatostatin receptors are also present in neuroendocrine gastroenteropancreatic tumors. Two long-acting somatostatin analogues, octreotide and lanreotide, are recognized by the receptor subtypes 2 and 5. Excessive hormone secretion in carcinoid syndrome can be controlled by these drugs. In addition, at least a subgroup of patients with carcinoid syndromes respond with delayed tumor growth during octreotide therapy. In the future, the availability of the somatostatin receptor cDNAs will allow the development of specific and even more potent receptor analogues.

Animals↗
PubMed2000

mRNA expression patterns of insulin-like growth factor system components in human neuroendocrine tumours.

BACKGROUND: Insulin-like growth factors (IGF) and their corresponding receptors and binding proteins are important in carcinogenesis for several tumours, but their expression pattern in the functionally and biologically heterogeneous human neuroendocrine tumours of the gastroenteropancreatic tract is largely unknown. MATERIALS AND METHODS: This study searched for the mRNA expression patterns of components of the IGF system: IGF-1 and IGF-2, IGF receptors 1 and 2 (IGF-1R, IGF-2R), IGF-binding proteins 1-6 (IGFBP1-6)) in the most frequent human gastroenteropancreatic neuroendocrine tumours (gastrinomas, insulinomas, tumours associated with carcinoid syndrome and functionally inactive tumours) employing reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: In the 37 tumour samples analysed (nine gastrinomas, 10 insulinomas, nine tumours associated with carcinoid syndrome and nine functionally inactive tumours) IGFBP-2 was found in all tumour samples while the IGFBP-1 was expressed only at low frequency (10-22%) among the four tumour types. The IGF-2R was predominantly expressed in gastrinomas. Among the four tumour types the expression of IGF-1R, IGF-2R and IGFBP-6 varied significantly. In addition, 12 pairs of significantly coexpressed IGF system components were detected (IGF-1 <--> IGF-1R, IGF-1 <--> IGF-2R, IGF-1 <--> IGFBP-3, IGF-1 <--> IGFBP-6, IGFBP-3 <--> IGF-1R, IGFBP-6 <--> IGF-1R, IGFBP-1 <--> IGF-2R, IGFBP-3 <--> IGF-2R, IGFBP-5 <--> IGF-2R, IGFBP-3 <--> IGFBP-5, IGFBP-3 <--> IGFBP-6, IGFBP-5 <--> IGFBP-6). CONCLUSIONS: The described differences of the expression patterns of the IGF system components in neuroendocrine tumour subtypes suggest tumour type-dependent different pathways in tumour growth control by IGF system components.

Gastrinoma↗
PubMed2000

Glucagon-like peptide-1 improves insulin and proinsulin binding on RINm5F cells and human monocytes.

Glucagon-like peptide-1-(7---36) amide (GLP-1) is a potent incretin hormone secreted from distal gut. It stimulates basal and glucose-induced insulin secretion and proinsulin gene expression. The present study tested the hypothesis that GLP-1 may modulate insulin receptor binding. RINm5F rat insulinoma cells were incubated with GLP-1 (0.01-100 nM) for different periods (1 min-24 h). Insulin receptor binding was assessed by competitive ligand binding studies. In addition, we investigated the effect of GLP-1 on insulin receptor binding on monocytes isolated from type 1 and type 2 diabetes patients and healthy volunteers. In RINm5F cells, GLP-1 increased the capacity and affinity of insulin binding in a time- and concentration-dependent manner. The GLP-1 receptor agonist exendin-4 showed similar effects, whereas the receptor antagonist exendin-(9---39) amide inhibited the GLP-1-induced increase in insulin receptor binding. The GLP-1 effect was potentiated by the adenylyl cyclase activator forskolin and the stable cAMP analog Sp-5, 6-dichloro-1-beta-D-ribofuranosyl-benzimidazole-3', 5'-monophosphorothioate but was antagonized by the intracellular Ca(2+) chelator 1,2-bis(0-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM. Glucagon, gastric inhibitory peptide (GIP), and GIP-(1---30) did not affect insulin binding. In isolated monocytes, 24 h incubation with 100 nM GLP-1 significantly (P<0.05) increased the diminished number of high-capacity/low-affinity insulin binding sites per cell in type 1 diabetics (9,000+/-3,200 vs. 18,500+/-3,600) and in type 2 diabetics (15,700+/-2,100 vs. 28,900+/-1,800) compared with nondiabetic control subjects (25,100+/-2,700 vs. 26,200+/-4,200). Based on our previous experiments in IEC-6 cells and IM-9 lymphoblasts indicating that the low-affinity/high-capacity insulin binding sites may be more specific for proinsulin (Jehle, PM, Fussgaenger RD, Angelus NK, Jungwirth RJ, Saile B, and Lutz MP. Am J Physiol Endocrinol Metab 276: E262-E268, 1999 and Jehle, PM, Lutz MP, and Fussgaenger RD. Diabetologia 39: 421-432, 1996), we further investigated the effect of GLP-1 on proinsulin binding in RINm5F cells and monocytes. In both cell types, GLP-1 induced a significant increase in proinsulin binding. We conclude that, in RINm5F cells and in isolated human monocytes, GLP-1 specifically increases the number of high-capacity insulin binding sites that may be functional proinsulin receptors.

Adult↗
PubMed1999

A nutrient-regulated cytosolic calcium oscillator in endocrine pancreatic glucagon-secreting cells.

We investigated the influence of nutrients on spontaneous cytosolic calcium oscillations in InR1-G9 glucagonoma cells, a model for pancreatic alpha-cells. The oscillations depended on calcium release from stores and on calcium influx, partly through voltage-dependent calcium channels. Oscillations required the presence of at least 1 mM glucose, 50 microM alanine, or 50 microM glutamine, but were terminated by higher nutrient concentrations (40 mM glucose, or above 2 mM alanine or glutamine). The effects depended on the metabolism of the nutrients. Glutamine and alanine hyperpolarized the cells. This effect was inhibited (glutamine) or attenuated (alanine) by 1 mM ouabain. Our findings suggest that [Ca2+]i regulation in alpha-cells is dominated by slow oscillations induced by a lack of metabolic energy, resulting in decreased calcium export and storage, as well as increased calcium influx, partly due to depolarization caused by reduced sodium pump activity. These processes, leading to an elevated cytosolic calcium concentration, may mediate oscillations by calcium-induced calcium release from intracellular stores.

Alanine↗
PubMed1999

Plasma leptin levels do not change in healthy humans shortly after a hydrocortisone challenge.

The acute response of plasma leptin levels to a hydrocortisone challenge was measured in 16 healthy volunteers. We additionally asessed insulin which is known to play a regulatory role in the leptin system. While plasma cortisol levels increased significantly after the administration of hydrocortisone, this rise was not associated with any change in leptin and insulin concentrations during the 3.5-hour experimental period. This result corroborates the assumption that glucocorticoid-induced increases in leptin levels, as described in the literature, occur delayed and are due rather to an activation of leptin synthesis than to a mere leptin release.

Adult↗
PubMed1998

Effects of VIP and related peptides on airway mucus secretion from isolated rat trachea.

Vasoactive intestinal polypeptide (VIP) is known as an important regulator of airway function. It has been suggested that VIP is involved in the pathogenesis of asthma due to its relaxant effects on smooth muscles. The present study was designed to characterize the effects of the peptides of the VIP family on airway mucus secretion. The peptides VIP, PHI, PACAP-27, PACAP-38, GLP-I, exendin-4, helodermin, helospectin I and helospectin II were investigated using isolated rat trachea. Data show that PACAP-27 is the most potent stimulator of airway mucus secretion (225% stimulation). The rank order of potency was PACAP-27 > VIP > helospectin II > PHI > exendin-4 = helodermin = helospectin I = PACAP-38. The addition of the protease inhibitor thiorphan enhanced the effects of PHI and helodermin, but not of the other peptides. These data show that the peptides of the VIP family stimulate airway mucus secretion differently.

Animals↗
PubMed1998

High-level expression of the GLP-I receptor results in receptor desensitization.

Glucagon-like peptide-I (GLP-I) is a potent insulinotropic incretin hormone. Since the insulinotropic action of GLP-I is preserved in patients with diabetes mellitus, the peptide is now tested as new therapeutic agent for the treatment of diabetes. The number of GLP-I receptors present on B cells is regulated by several signal transduction pathways. In this study, we generated several Chinese hamster ovary (CHL) cell lines stably expressing different numbers of GLP-I receptors. The effects on binding properties and signal transduction were characterized. The lowest number of receptors was 1,791 per cell; the highest was 378,720 per cell. A comparable affinity against GLP-I was obtained with all clones. The three clones with the lowest numbers of receptors (1,791, 4,371, and 5,633 per cell) did not show any cyclic AMP (cAMP) generation in response to GLP-I (1 pM-1 microM). Cells expressing 13,175, 41,872, 271,003, and 378,720 receptors, respectively, increased cAMP concentration-dependently after GLP-I. The cell line with the highest number of receptors had the maximal response (352% of controls) but a dramatically reduced EC50 (100 nM, compared to 8 and 7 nM). All cell lines showed an identical cAMP response to 1 and 10 microM forskolin. These data demonstrate that a minimum number of GLP-I receptors is required for signal transduction. The GLP-I receptor is desensitized when expressed in high numbers on the cells. In this case, the signal transduction properties remain unchanged.

Animals↗
PubMed1997

Leptin inhibition of insulin secretion from isolated human islets.

Leptin is a hormone produced and secreted from the adipose tissue. Its physiological actions include the regulation of satiety, food intake and energy balance. The production of leptin is increased by high insulin levels. Here, we demonstrate that leptin acts as an inhibitor of glucose-induced (20 mM) insulin secretion from isolated human islets. No effect was observed in the presence of lower glucose levels (2.8 and 10 mM glucose). The pancreatic beta-cell might represent a target of a direct physiological action of leptin. We suggest the presence of an "adipo-insular axis" in which leptin mediates negative feedback from the adipose tissue to the endocrine pancreas.

Animals↗
PubMed1997

Incretin hormone expression in the gut of diabetic mice and rats.

To elucidate the question of whether production of the insulinotropic gut hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) is altered by a diabetic metabolic state, their intestinal expression pattern was evaluated. Two rodent models for diabetes mellitus were used, non-obese diabetic (NOD) mice as a model for insulin-dependent diabetes and Zucker diabetic fatty (ZDF) rats for non-insulin-dependent diabetes mellitus (NIDDM). Expression of both incretin hormones followed typical patterns, which were similar in both animals and unaltered by the diabetic state. The GIP gene was greatly expressed in the duodenum, jejunum, and ileum, with a continuous decrease from the upper to lower intestines. This pattern was observed in both NOD mice and ZDF rats regardless of the diabetic state. This expression data was corroborated by radioimmunoassay (RIA) analysis of the gene product GIP. Expression of the proglucagon gene encoding GLP-1 had an opposite appearance. The highest expression was seen in the large bowel and the ileum. RIA analysis of the gene product GLP-1 mirrored these data. Although the distribution pattern was similar in both animal models, in contrast to diabetic NOD mice, a regulated expression was found in diabetic ZDF rats. Compared with lean nondiabetic controls, fatty hyperglycemic animals showed an increased expression of the proglucagon gene in the colon and a concomitant reduction in the small intestine. This was mirrored by the GLP-1 content of the colon and ileum. Overall, basal GLP-1 plasma levels were increased in ZDF rats (17.0 +/- 2.8 pmol) compared with lean Zucker rats (12.4 +/- 1.8 pmol). In conclusion, incretin hormone expression (GIP and GLP-1) follows specific patterns throughout the gut and is unaltered by the diabetic state. In ZDF rats, regulation of proglucagon expression occurs mainly in the large intestine.

Animals↗
PubMed1997

Leptin: a potent inhibitor of insulin secretion.

The hormone leptin is expressed and secreted by the adipose tissue and impacts on the central nervous system. Leptin is involved in the regulation of energy balance, satiety, and body composition. The lack of active leptin results in obesity, high food intake, hyperglycemia, and hyperinsulinemia. We present data supporting effects of leptin on the endocrine pancreas. We found the leptin receptor to be expressed in insulin- and glucagon-secretin cells derived from mouse, hamster, and rat pancreas. In the isolated perfused rat pancreas leptin is a potent inhibitor of basal and glucose-induced insulin secretion, especially during the first phase of the insulin response. At isolated mouse islets and insulin-secreting INS-1 cells leptin reduced promptly and persistently the intracellular Ca2+ levels. Cytoplasmic Ca2+ oscillation amplitude was decreased and the oscillation frequency increased. These findings suggest functional active receptors for leptin on insulin-secreting B-cells. Therefore, leptin is a metabolic hormone and not only a signal to the brain indicating filled fat stores. Our data suggest that leptin is also a signal back to the endocrine pancreas that no more insulin is required to replenish fat stores. Thus, an "adipo-insular axis" operating with two arms exists: insulin and glucagon are signals to the adipocyte. This releases leptin, which could be the mediator of the respective feedback to the pancreas. A defective leptin suppression of insulin secretion could contribute to hyperinsulinemia and disturbances of glucose metabolism.

Animals↗