Circulating growth hormone forms in Type 1 diabetic subjects: comparison with normal subjects and acromegalics

1986 ◽  
Vol 112 (4) ◽  
pp. 547-551 ◽  
Author(s):  
L. A. MacFarlane ◽  
Susan Stafford ◽  
A. D. Wright

Abstract. The molecular forms of growth hormone (GH) in serum from 18 Type 1 diabetic patients with poor metabolic control were analysed using sephadex G-100 chromatography. The profiles obtained were compared with those from normal subjects whose GH secretion was stimulated by exercise and hypoglycaemia and eight acromegalic patients. In the three groups three distinct GH forms were found: little (monomeric), big and big-big-GH. Samples from normal subjects contained 45% little-GH which was less than samples from the diabetics and acromegalics (53% and 65%, respectively, P <0.01). Further samples from normal subjects after the onset of hypoglycaemia showed an increase in little-GH. In the three groups, the higher the proportion of little-GH, the lower the proportion of big-big-GH, while the proportion of big-GH remained similar. In the acromegalics the proportion of little-GH was strongly correlated with the log concentration of serum GH. As little-GH is cleared from the circulation quicker than the larger forms these data indicate that the main component of the frequent surges of GH secretion in poorly controlled Type 1 diabetic subjects is little-GH (monomeric forms). The sustained release of GH found in acromegaly is composed largely of monomeric forms.

1990 ◽  
Vol 71 (6) ◽  
pp. 1486-1490 ◽  
Author(s):  
ANDREA GIUSTINA ◽  
SIMONETTA BOSSONI ◽  
ANTONINO CIMINO ◽  
GIUSEPPE PIZZOCOLO ◽  
GIUSEPPE ROMANELLI ◽  
...  

1993 ◽  
Vol 264 (5) ◽  
pp. E756-E762 ◽  
Author(s):  
P. Nuutila ◽  
J. Knuuti ◽  
U. Ruotsalainen ◽  
V. A. Koivisto ◽  
E. Eronen ◽  
...  

To determine the tissue localization of insulin resistance in type 1 diabetic patients, whole body and regional glucose uptake rates were determined under euglycemic hyperinsulinemic conditions. Leg, arm, and heart glucose uptake rates were measured using positron emission tomography-derived 2-deoxy-2-[18F]-fluoro-D-glucose kinetics and the three-compartment model described by Sokoloff et al. (L. Sokoloff, M. Reivich, C. Kennedy, M.C. DesRosiers, C.S. Patlak, K.D. Pettigrew, O. Sakurada, and M. Shinohara. J. Neurochem. 28: 897–916, 1977) in eight type 1 diabetic patients and eight matched normal subjects. Whole body glucose uptake was quantitated by the euglycemic insulin clamp technique. Whole body glucose uptake was approximately 31% lower in the diabetic patients (P < 0.01) than in the normal subjects, thus confirming the presence of whole body insulin resistance. The rate of glucose uptake was approximately 45% lower in leg muscle when measured in the femoral region (55 +/- 7 vs. 102 +/- 13 mumol.kg muscle-1.min-1, diabetic patients vs. normal subjects, P < 0.05) and approximately 27% lower in the arm muscles (66 +/- 4 vs. 90 +/- 13 mumol.kg muscle-1.min-1, respectively, P < 0.05), whereas no difference was observed in heart glucose uptake [789 +/- 80 vs. 763 +/- 58 mumol.kg muscle-1.min-1 not significant (NS)]. Whole body glucose uptake correlated with glucose uptake in femoral (r = 0.93, P < 0.005) and arm muscles (r = 0.66, P < 0.05) but not with glucose uptake in the heart (r = 0.04, NS). We conclude that insulin resistance in type 1 diabetic patients is localized to skeletal muscle, whereas heart glucose uptake is unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)


1991 ◽  
Vol 125 (5) ◽  
pp. 510-517 ◽  
Author(s):  
Andrea Giustina ◽  
Simonetta Bossoni ◽  
Corrado Bodini ◽  
Antonino Cimino ◽  
Giuseppe Pizzocolo ◽  
...  

Abstract. We evaluated the effects of iv pretreatment with exogenous GH on the GH response to GHRH either alone or in combination with pyridostigmine in 14 Type I diabetic patients and 6 normal subjects. All the subjects received an iv bolus injection of biosynthetic human GH, 2 IU; 2 h later they received either a. pyridostigmine, 120 mg orally, or b. placebo, 2 tablets orally, followed 1 h later by iv injection of GHRH(1-29) NH2, 100 μg. In normal subjects the median GH peak after GH+GHRH was 1.8, range 1.2-6.9 μg/l. Pyridostigmine enhanced the GH response to GHRH in all subjects. The median GH peak after pyridostigmine+ GH+GHRH was 32.7, range 19.8-42.1 μg/l (p<0.001 vs GHRH alone). Seven diabetic subjects had median GH peaks after GH+GHRH >6.9 μg/l (the maximum GH peak after GH+GHRH in normal subjects) (group A: median GH peak 35.7, range 21.7-55 μg/l). The other diabetic subjects had GH peak lower than 6.9 μg/l (group B: median GH peak 4.4, range 2.1-6.5 μg/l). Pyridostigmine significantly increased the GH response to GHRH in group B patients (median GH peak 29.3, range 15.7-93.4 μg/l, p<0.001 vs GH+GHRH alone), but not in group A patients (median GH peak 39.9, range 21.9-64.9 μg/l). Group A diabetic patients were younger and had higher HbA1c and blood glucose levels than group B patients. In those diabetic patients with an exaggerated GH response to GH+GHRH, pyridostigmine failed to cause the increase in GH secretion observed in diabetic and control subjects with no responses to GH+GHRH. It can be suggested that elevated 24-h GH levels in some Type I diabetic patients may be due to decreased somatostatinergic tone which in turn causes altered autoregulation of GH secretion. We hypothesize that this finding is a consequence of a reset of the hypothalamic control of GH secretion caused by a chronically elevated blood glucose level in this subpopulation.


2001 ◽  
Vol 59 (6) ◽  
pp. 2104-2113 ◽  
Author(s):  
Michael W. Steffes ◽  
Derek Schmidt ◽  
Rebecca Mccrery ◽  
John M. Basgen

2006 ◽  
Vol 91 (9) ◽  
pp. 3507-3514 ◽  
Author(s):  
Lucia Puricelli ◽  
Elisabetta Iori ◽  
Renato Millioni ◽  
Giorgio Arrigoni ◽  
Peter James ◽  
...  

Abstract Context: Protein profiling of diabetic tissues could provide useful biomarkers for early diagnosis, therapeutic targets, and disease response markers. Cultured fibroblasts are a useful in vitro model for proteome analysis and study of the molecular mechanisms involved in diabetes. Objective: The objective of the study was to isolate and characterize the proteins of cultured fibroblasts, obtained by skin biopsy, from long-term type 1 diabetic patients without complications and age- and sex-matched normal subjects as controls. Design: Proteins were separated by two-dimensional electrophoresis (2-DE), and the gel images were qualitatively and quantitatively analyzed. Protein identification was performed by matrix-assisted laser desorption/ionization mass spectrometry. Results: Reproducible protein maps of fibroblasts from diabetic and healthy subjects were obtained. A total of 125 protein spots were isolated and identified, among them 27 proteins not previously reported in published human fibroblast 2-DE maps, including 20 proteins never reported previously in the literature in human skin fibroblasts. Quantitative analyses revealed six protein spots differentially expressed in the fibroblasts from the diabetic vs. the control subjects (P &lt; 0.05), representing glycolytic enzymes and structural proteins. An increase of triosephosphate I isomerase of two splice isoforms of pyruvate kinase and α-actinin 4 and a decrease of tubulin-β2 and splice isoform 2 of tropomyosin β-chain were detected. Conclusions: We generated 2-DE reference maps of the proteome of human skin fibroblasts from both normal and uncomplicated type 1 diabetic patients. Differences in glycolytic enzymes and structural proteins were found. The functional implications of the identified proteins are discussed.


1974 ◽  
Vol 76 (3) ◽  
pp. 488-494 ◽  
Author(s):  
M. Peracchi ◽  
F. Cavagnini ◽  
A. E. Pontiroli ◽  
U. Raggi ◽  
A. Malinverni ◽  
...  

ABSTRACT The effects of intravenously administered aminophylline on growth hormone (GH) secretion have been studied in sixteen normal subjects and four acromegalic patients. Intravenous infusion of theophylline ethylenediamine 480 mg over a 30 min period did not alter the blood glucose and serum GH levels in six normal subjects but raised the plasma FFA by 88 %. By contrast, in four acromegalic patients theophylline administration resulted in a fall of the serum GH levels by 17.6–51.7 %, mean 36.5%. In ten normal subjects the infusion of the drug clearly blunted the GH response to insulin hypoglycaemia without modifying the decrease in blood glucose and plasma FFA induced by insulin: mean peak GH values decreased from 32.7 ± 3.39 to 21.4 ± 4.10 ng/ml (P < 0.025). These data seem to indicate that theophylline has an overall inhibiting effect on the hypothalamic-hypophyseal axis for GH secretion.


1974 ◽  
Vol 61 (2) ◽  
pp. 219-229 ◽  
Author(s):  
Y. N. SINHA ◽  
F. W. SELBY ◽  
W. P. VANDERLAAN

SUMMARY The secretion of prolactin and growth hormone (GH) in C3H/St mice, a strain having a high incidence of spontaneous mammary tumours, was studied at intervals throughout pregnancy and lactation. Serum and pituitary concentrations of prolactin and GH were measured by specific, homologous radioimmunoassays. Crude extracts of mouse placentae did not cross-react in these assays, indicating that the assay systems measured prolactin and GH of hypophysial origin. Except for a small, brief rise on day 5, prolactin secretion was low throughout most of pregnancy; the serum concentration of prolactin increased appreciably only near term. During lactation, prolactin in serum averaged from 5 to 10 times basal levels (30–40 ng/ml) until day 15 of lactation, after which the concentration declined. In contrast, GH secretion increased early in pregnancy, the concentration rising both in serum and in the pituitary gland consistently after day 5. The serum concentrations reached 3–10 times basal levels (8–12 ng/ml) between days 10 and 20 of pregnancy. There were successive decreases in serum GH concentration after parturition; the concentration reached basal levels on day 5, but it increased thereafter and was maintained at over three times basal levels for the remainder of lactation. The levels of GH in serum were highly correlated with mammary DNA and RNA contents during pregnancy, while prolactin concentration was more strongly correlated with mammary function during lactation.


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