PubMed Health⌕ Search

Biomedical subjects

H C Fehmann

Publications and source records attributed to H C Fehmann.

At least 37 records · Page 2Linked to original sources
PubMed1997

No apparent benefit of liquid formula diet in NIDDM.

We have studied the impact of liquid diets formulated for complete or supplemental enteral nutrition of type II, non insulin-dependent (NIDDM) diabetics on carbohydrate homeostasis. To achieve this, liquid formula tolerance tests were performed in NIDDM patients under an oral treatment regimen with a combination of diet plus glibenclamide (7 men, 3 women, age: 56 +/- 11 years; mean body mass index of 26.2 +/- 3.6 kg/m2). After an overnight fast, each patient received the usual morning medication and, thereafter, ingested formula diet in randomized order with 10 day intervals between tests. 500 ml were administered of either a standard liquid diet (Biosorb Sonde), a fibre containing diet (Biosorb Plus Sonde), or a carbohydrate modified, fructose containing "diabetes" diet (Fresubin Diabetes) (carbohydrate contents of approximately equal to 60 g, respectively). Blood samples were collected over 180 min. Considering minor variations in the nutritional values of the diets, IR-insulin, IR-C-peptide, IR-glucose-dependent insulinotropic polypeptide (GIP), and IR-glucagon-like peptide. 1 (GLP-1) in plasma did not significantly differ between the study groups. After ingestion of Biosorb Sonde area under the curve glucose was greater than that seen after uptake of fibre containing or carbohydrate modified, i.e. fructose containing "liquid diabetes diets". All diets challenged the entero-insular axis in non-insulin dependent diabetics to a comparable extent. This data does not support the contention to employ special "diabetes" formulas for enteral nutrition of patients with NIDDM.

Adult↗
PubMed1997

Interaction of GLP-I and leptin at rat pancreatic B-cells: effects on insulin secretion and signal transduction.

The incretin effect is reduced in NIDDM, although a corresponding attenuation of incretin hormone secretion does not occur. We characterized the direct interaction of GLP-I, an important incretin hormone, and leptin on insulin secretion and signal transduction in B-cells. Leptin inhibited GLP-I stimulated insulin release from the isolated perfused rat pancreas. Both phases of the biphasic insulin secretory response were inhibited. GLP-I receptor binding and GLP-I induced cAMP generation remained unchanged. Leptin reduced the GLP-I mediated increase of cytosolic Ca2+ concentration. It had similar effects on calcium elevations induced by forskolin. The effect was more pronounced during the plateau phase than during the initial peak. These effects could help to explain leptin's inhibitory effects on insulin secretion. The inhibition of GLP-I's insulinotropic effects by leptin may be an interesting aspect in the pathophysiology of NIDDM. The existence of an "adipo-insular axis" is suggested, in which leptin represents a negative feed-back signal from the adipose tissue to the endocrine pancreas.

Animals↗
PubMed1997

[The intestinal hormone glucagon-like peptide 1 (GLP-1): from experiment to the clinic].

A functional connection between the small intestine and endocrine pancreas was proved in the sixties, after it became possible to determine the exact amount of insulin in plasma. The insulin response after oral doses of glucose is substantially stronger than after intravenous doses of sugar, even when identical glucose plasma levels are attained. This incretin effect is explained by the connection of the entero-insular axis. The intestinal hormones, that are released by the small intestine after meals, circulate measurably in plasma, and strengthen the glucose-induced insulin secretion, are responsible for this effect. In addition to the classical incretin hormone "Gastric inhibitory polypeptide-1" (GIP), "Glucagon-like peptide-1" (GLP-1) is very interesting to investigators today. In a relatively short amount of time, GLP-1 has matured from a physiologically interesting incretin hormone candidate to a potentially therapeutical alternative for the treatment of diabetes mellitus. GLP-1 stimulates glucose-dependent insulin secretion, decreases plasma glucagon levels, delays gastric emptying, and putatively exerts an additional effect on peripheral glucose utilization. On top of that, GLP-1 has effects on the central nervous system thereby impacting on feeding behavior.

Animals↗
PubMed1996

Effects of selective and non-selective phosphodiesterase inhibitors on tracheal mucus secretion in the rat.

The present study was designed to characterize the effects of unselective and isoenzyme-selective phosphodiesterase inhibitors on airway mucus secretion. The isolated rat trachea was incubated in a modified Ussing chamber. Mucus macromolecules were metabolically labelled with 35S. The inhibitors were applied at the luminal side. The unselective phosphodiesterase inhibitors theophylline, enprofylline and 3-isobutyl-methylxanthine stimulated mucus secretion in a concentration-dependent manner with half-maximum effects (EC50 values) at 690 microM, 400 microM and 46 microM, respectively. The adenosine antagonist 8-phenyltheophylline did not significantly stimulate mucus output, suggesting a negligible role of adenosine in the cellular mechanisms of mucus secretion. Adenosine itself did not increase radiolabel output. Rolipram, an inhibitor of phosphodiesterase isoenzyme IV, and zardaverine, which inhibits the isoenzymes III and IV, increased potently macromolecule output with EC50 values of 40 nM and 6 microM, respectively. The selective inhibitors of phosphodiesterase isoenzymes III and V, motapizone and zaprinast, did not influence airway mucus release, suggesting a relatively low activity of isoenzymes III and V in glands of rat trachea. The stimulatory effect of theophylline on airway mucus secretion may contribute to its beneficial action in chronic obstructive airway disease. Our data suggest that this effect is mediated predominantly by phosphodiesterase isoenzyme IV.

1-Methyl-3-isobutylxanthine↗
PubMed1996

Regulation of glucagon-like peptide-I receptor expression and transcription by the protein kinase C pathway.

Glucagon-like peptide-I (GLP-I) is an important insulinotropic incretin hormone. The GLP-I receptor belongs to the family of seven transmembrane domain receptors. We studied the regulation of its expression by the protein kinase C (PKC)-dependent pathway in rat insulinoma RINm5F cells. Cells were incubated for 3, 6 and 24 h with an optimal concentration of tissue plasminogen activator (TPA), an activator of PKC. TPA induced significantly lower GLP-I receptor mRNA levels under steady-state conditions after 6 and 24 h. The stability of the GLP-I receptor mRNA was unchanged. The number of GLP-I receptors present on RINm5F cells was reduced after 6 and 24 h. TPA did not influence the affinity of remaining receptors to its specific ligand. These data indicate that PKC activation downregulates the expression of the GLP-I receptor gene, mainly at the transcriptional level.

Animals↗
PubMed1996

Functional active receptors for insulin-like growth factors-I (IGF-I) and IGF-II on insulin-, glucagon-, and somatostatin-producing cells.

Insulin-like growth factors I and II (IGF-I and IGF-II) are expressed at high levels in the endocrine pancreas during development and tissue regeneration. However, their effects at the endocrine pancreas are poorly understood. We searched for receptors of IGF-I and IGF-II and possible biological effects on clonal insulin-secreting (HIT), glucagon-secreting (INR1G9), and somatostatin-secreting (RIN 1027 B2) cell lines. Our data showed that HIT cells and RIN 1027 B2 cells express specific type I and type 11 IGF receptors. INR1G9 cells possess type II IGF receptors and IGF-I binding sites with the same affinity for both IGF-I and IGF-II. In HIT cells, insulin secretion was not influenced by either peptide. Proinsulin gene transcription was stimulated by IGF-II but not by IGF-I. IGF-I potently inhibited proglucagon gene transcription and glucagon secretion in INR1G9 cells, whereas IGF-II only inhibited glucagon release. In RIN 1027 B2 cells, IGF-I but not IGF-II increased somatostatin output, whereas both stimulated somatostatin gene expression. These data demonstrate the presence of classic type I and type II IGF receptors on insulin-, glucagon-, and somatostatin-secreting cells. Both peptides may be important regulators of endocrine pancreatic function in terms of islet hormone release and gene expression. Therefore, both peptides may be involved in the regulation of intraislet cellular homeostasis.

Animals↗
PubMed1996

Insulin and insulin-like growth factor-I: their role as risk factors in the development of diabetic cardiovascular disease.

Experimental data support a role for insulin and insulin-like growth factor-I (IGF-I) in the pathophysiology of vascular complications in diabetes. Clinical data for both hormones are less convincing, mainly because the various studies vary in methodologies, sample sizes, and populations. So far, by epidemiological means, insulin's vascular toxicity has been shown only in middle-aged non-diabetic men. Furthermore, serious methodological problems hamper the clear understanding of IGF-I's significance in this context. Definitive determination of the role of insulin, IGFs and other growth factors in the development of diabetic vascular complications needs considerably more work. In any case, hyperinsulinemia is associated with a cluster of other accepted risk factors for cardiovascular disease which altogether resemble the entire insulin-resistance syndrome.

Cardiovascular Diseases↗
PubMed1996

Ligand-induced regulation of glucagon-like peptide-I receptor function and expression in insulin-secreting beta cells.

Glucagon-like peptide-I (GLP-I) is a potent incretin hormone and mediates its actions via the cyclic AMP (cAMP) pathway. The GLP-I receptor belongs to the family of seven-transmembrane domain receptors coupled to G proteins. We have analyzed the regulation of GLP-I receptor function and expression by its own ligand and the cAMP-dependent pathway in rat insulinoma-derived beta cells (RINm5F). The GLP-I receptor underwent rapid homologous desensitization, which occurred at the receptor level. This was characterized by a reduced binding capacity not mediated by protein kinase A (PKA). GLP-I receptor mRNA levels were down-regulated during incubation of cells by agents increasing cAMP levels including GLP-I itself. This effect was dependent upon time and concentration. Forskolin, the PKA activator 5,6-dichloro-1-beta-D-ribofuranosyl-benzimidazole-3, 5-monophosphorothiotate, and GLP-I stabilized the GLP-I receptor mRNA. All induced down-regulation of the GLP-I receptor number within 3 h, a time point at which GLP-I receptor mRNA levels were not decreased. This effect was not influenced by cycloheximide. Therefore, in addition to transcriptional effects, posttranslational mechanisms exist to regulate GLP-I receptor numbers in insulin-secreting cells.

Animals↗
PubMed1996

[Molecular biology, pharmacology and signal transduction of 5 cloned human somatostatin receptors].

Somatostatin is a hormone with inhibitory properties, which is expressed in several tissues including the gastrointestinal tract. Actually, somatostatin and somatostatin-analogues are used for the treatment of neuroendocrine tumors and esophageal varices. Somatostatin acts via specific receptors. So far, five somatostatin receptor subtypes have been isolated and cloned. They are characterized by a high degree of sequence homology. The different receptor subtypes recognize the naturally occurring and the pharmaceutically developed ligands with different affinities. The receptor subtypes are expressed in a tissue-specific manner and in different tissues they couple to different signal-transduction pathways. The somatostatin receptors are also expressed in several malignant tissues. But the expression pattern varies from tumor to tumor. The availability of the receptors and their cDNAs allows the characterization of somatostatin's molecular action in greater detail. The design of even more potent somatostatin anlogues seems possible as well as the development of new therapeutical strategies.

Amino Acid Sequence↗
PubMed1995

Molecular cloning, functional expression, and signal transduction of the GIP-receptor cloned from a human insulinoma.

Glucose-dependent insulinotropic polypeptide (GIP) plays an important role in the regulation of postprandial insulin secretion and proinsulin gene expression of pancreatic beta-cells. This study demonstrates the molecular cloning of a cDNA for the GIP-receptor from a human insulinoma lambda gt11 cDNA library. The cloned cDNA encoded a seven transmembrane domain protein of 466 amino acids which showed high homology (41%) to the human glucagon-like peptide 1 (GLP-1) receptor. Homology to the GIP receptor from rat or hamster was 79% and 81%, respectively. When transfected stably into fibroblast CHL-cells a high affinity receptor was expressed which coupled to the adenylate cyclase with normal basal cAMP and increasing intracellular cAMP levels under stimulation with human GIP-1-42 (EC50 = 1.29 x 10(-13) M). The receptor accepted only human GIP 1-42 (Kd = 1.93 +/- 0.2 x 10(-8) M) and porcine truncated GIP 1-30 (Kd = 1.13 +/- 0.1 x 10(-8) M) as high affinity ligands. At 1 microM, exendin-4 and (9-39)amide weakly reduced GIP-binding (25%) whereas secretin, glucagon, glucagon-like peptide-1, vasoactive intestinal polypeptide, peptide histidine-isoleucine, and pituitary adenylyl cyclase activating peptide were without effect. In transfected CHL cells, GIP-1-42 did not increase intracellular calcium. Northern analysis revealed one transcript of human GIP receptor mRNA with an apparent size of 5.5 kb. The exact understanding of GIP receptor regulation and signal transduction will aid in the understanding of the incretin hormone's failure to exert its biological action at the pancreatic B-cell in type II diabetes mellitus.

Amino Acid Sequence↗
PubMed1995

The glucagon gene is transcribed in beta-like pancreatic cells.

In this report we demonstrate that approximately 1.1 kb of the rat glucagon gene promoter upstream of the transcriptional start site specifically directs the transcription of the reporter gene chloramphenicol acetyl transferase (CAT) (p[-1.1]GLU-CAT) in insulinoma beta-TC1 cells. On the contrary, the 350 bp closest to the transcription start site (p[-0.35]GLU-CAT) are ineffective in beta-TC1 cells. Both constructs are transcriptionally active in InR1-G9 glucagonoma cells. While protein kinase A and protein kinase C activators, acting through independent pathways, strongly increase both the transcription of p[-1.1]GLU-CAT and the accumulation of glucagon transcript in beta-TC1 cells, they are weaker activators in InR1-G9 cells. Our experiments suggest that some positive transcription control elements, necessary for the glucagon gene transcription in insulinoma beta-TC1 cells, are localized in the -350/-1100 region of the glucagon gene. Furthermore, our data indicate that glucagon gene transcription can be strongly activated through the protein kinase A pathway in some specific cellular contexts.

Animals↗
PubMed1995

Interaction of glucagon-like peptide-I (GLP-I) and galanin in insulin (beta TC-1)- and somatostatin (RIN T3)-secreting cells and evidence that both peptides have no receptors on glucagon (INR1G9)-secreting cells.

The interaction of glucagon-like peptide-I (GLP-I) and galanin in clonal endocrine pancreatic cells was characterized. By Northern blot analysis the presence of GLP-I receptor mRNA was shown in B (beta TC-1 cells) and D (RIN 1048-38) cells but not in A (INR1 G9) cells, thus confirming functional data demonstrating the absence of active GLP-I receptors on glucagon-producing cells. Galanin receptors were detected on B and D cells but not on A cells. In B and D cells galanin inhibited the GLP-I stimulated adenylate cyclase activity. Treatment of insulin- and somatostatin-producing cells with GLP-I increased intracellular cAMP levels, and this was dampened by galanin, GLP-I stimulated the activity of protein kinase A in B and D cells, which was also inhibited by galanin. Galanin alone did not influence B- and D-cell function. These data show that in the endocrine pancreas B and D cells but not A cells express GLP-I and galanin receptors. The interaction of GLP-I and galanin might act in the endocrine pancreas as a physiological inhibitor of the potent incretin hormone GLP-I. Therefore, we suggest galanin is a 'decretin'.

Animals↗
PubMed1995

Amylin immunoreactivity in the rat trachea and characterization of the interaction of amylin and somatostatin on airway mucus secretion.

Amylin is a peptide containing 37 amino acids that is mainly expressed in pancreatic B-cells and cosecreted with insulin. It is the major component of the islet amyloid typically found in non-insulin-dependent diabetes mellitus. The amylin mRNA is present in RNA isolated from lung, and amylin receptors have been detected in lung membranes. Recently, amylin was shown to be a potent stimulator of airway mucus secretion. In this study, we characterized the site of amylin expression in rat trachea using a highly specific antiserum and the functional interaction of amylin with somatostatin-14 in mucus secreting cells. Amylin-like immunoreactivity is present in epithelial cells of submucous gland acini. The expression pattern varies, since some acini showed strong staining while others were negative. In addition, some columnar cells of the tracheal lining epithelium are strongly stained. Amylin applied submucosally is a potent stimulator of airway mucus secretion. Somatostatin inhibits this effect. Amylin may influence airway mucus secretion by paracrine and endocrine mechanisms, and our data suggest that amylin and somatostatin belong to the increasing number of peptides that are known to influence airway function.

Amyloid↗
PubMed1995

Galanin and somatostatin inhibition of neurokinin A and B induced airway mucus secretion in the rat.

Neurokinin A and B are present in neurons situated in lung and NK-1 receptors have been described on tracheal submucosal gland cells. In the present study we compared the ability of substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) to stimulate airway mucus secretion. Furthermore, we characterized the interaction of NKA and NKB with galanin and somatostatin. The rank order of the tachykinins to stimulate airway mucus secretion was SP > NKA > NKB suggesting that NK-1 receptors mediate these effects(EC50:SP: 50 nmol/l, NKA: 200 nmol/l, NKB: 400 nmol/l). Galanin and somatostatin were equally potent to inhibit NK-A and NK-B stimulated airway mucus release. These results suggest that NK-A and NK-B are potent stimulators of airway macromolecule secretion. Galanin and somatostatin potently inhibit these actions of the tachykinins. Therefore, airway mucus secretion is controlled by a complex network of several different mediators.

Animals↗