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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The direct influence of indoleamines on ovarian peptide hormones and growth factor secretion, in contrast to steroidogenesis, is yet to be thoroughly investigated. The aim of our in vitro experiments was to investigate the influence of melatonin and serotonin (5-hydroxy-tryptamine) (0.01-10 micrograms/ml) on the release of insulin-like growth factor-I (IGF-I), oxytocin and progesterone by cultured human granulosa cells. It was observed that both melatonin and serotonin stimulate IGF-I release. Melatonin also stimulated oxytocin output. Serotonin increased oxytocin secretion only at the highest dose (10 micrograms/ml). Both melatonin and serotonin were potent inhibitors of progesterone release. The present results suggest a possible involvement of the indoleamines melatonin and serotonin in the direct regulation of growth factor, nonapeptide and steroid hormone secretion by human ovarian cells.
Exp Clin Endocrinol Diabetes 1997
PMID:Melatonin and serotonin regulate the release of insulin-like growth factor-I, oxytocin and progesterone by cultured human granulosa cells. 913 42

Long-term diabetes in female rats preserves the bone mineral density (BMD) but impairs the strength of the femur. In this study, we have compared the effects of diabetes and high-dose 17 beta-estradiol (E2), two conditions of low bone formation, in ovariectomized (ovx) rats. Spontaneously diabetic BB rats were ovx 0-3 days after onset, and nondiabetic ovx littermates were used as controls; the rats were either untreated or treated with E2 (30 micrograms/day, subcutaneously), for 6 or 12 weeks (n = 9 in each of the eight groups). Analysis included: plasma 1,25-dihydroxyvitamin D3, insulin-like growth factor-I (IGF-I), and osteocalcin concentrations; histomorphometry of the proximal tibial metaphysis (PTM); and DXA and biomechanical testing of the femur. Both E2 treatment and diabetes markedly lowered plasma IGF-I and osteocalcin concentrations, as well as dynamic morphometric parameters of bone formation in the PTM. Plasma IGF-I and osteocalcin were correlated (R2 = 0.55; p < 0.0001). E2 treatment in both control and diabetic ovx rats increased the trabecular bone volume in the PTM and the BMD in the metaphysis of the distal femur; there was no difference between control and diabetic rats, however. The diaphyseal area and BMC were decreased in E2-treated or/and diabetic ovx rats, but the diaphyseal BMD remained unchanged compared with untreated ovx rats. The biomechanical properties of the whole femur (strength, angular deformation, and stiffness) were decreased in E2-treated and diabetic E2-treated ovx rats after 12 weeks. The data indicate that in situations of chronic low bone formation, whole bone strength does not reflect total BMD but correlates better with bone size and bone mineral content measurements.
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PMID:Effects of long-term diabetes and/or high-dose 17 beta-estradiol on bone formation, bone mineral density, and strength in ovariectomized rats. 914 39

We surveyed the clinical presentation, initial management and subsequent course of a prospectively registered cohort of 60 children with insulin-dependent diabetes mellitus (IDDM) diagnosed before age 15 years in the Sultanate of Oman between January 1990 and December 1993. Clinical details from the time of diagnosis were available on all the children. At diagnosis 9 (15 per cent) presented with severe ketoacidosis (DKA) with pH less than 7.1 or plasma bicarbonate less than 10 mmol/l, and 16 (27 per cent) had mild to moderate ketoacidosis with pH 7.1-7.35 or plasma bicarbonate 10-18 mmol/l. During DKA electrolyte disturbances included: hypokalemia (K < 3.5 mmol/l) 25 per cent), hyperkalemia (K > 5.5 mmol/l) (18 per cent) and hyponatremia (Na < 130 mmol/l) (40 per cent). Serum creatinine concentrations were high in 25 per cent of children with DKA. Within the first year of diagnosis, 17 of the 60 children (28 per cent) experienced symptomatic hypoglycaemia, which in six (10 per cent) led to one or more admissions. Re-admission for unstable glycaemic control, excluding acute hypoglycaemia occurred at least once in six children (10 per cent) within 1 year of diagnosis and in 10 (17 per cent) within 2 years. Statural growth velocity (GV) and GVSDS (6.9 +/- 0.85 cm/year and 0.75, respectively) were significantly higher in the group of children with good glycaemic control (HbA1C = 7.9 +/- 0.4 per cent) compared to those children (3.7 +/- 0.44 cm/ year and -1.6, respectively) with bad glycaemic control (HbA1C = 12.5 +/- 1.5 per cent). Insulin-like growth factor-I (IGF-I) concentrations were significantly higher (260 +/- 21 ng/ml) in the group with good glycemic control v. the group with bad control (149 +/- 15 ng/ml). In summary, greater public and medical awareness of the presenting features of diabetes in young children is needed to reduce the frequency of DKA at presentation, and improvement of patient and family education is necessary to reduce the incidence of DKA and hypoglycaemia in children with IDDM.
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PMID:Mode of presentation and progress of childhood diabetes mellitus in the Sultanate of Oman. 923 30

Insulin-like growth factor-I (IGF-I) is a pleiotropic protein that acts on many tissues and organs. As it is one of the major trophic factors in the circulation, its actions in peripheral tissues are well established. It has been used for the treatment of several diseases, including growth deficiency, osteoporosis, catabolic disorders and diabetes. Recent evidence supports the significance of IGF-I in the maintenance of the integrity and homeostasis of the nervous system. The widespread distribution of its receptor allows IGF-I to affect the survival of numerous populations of neurones and glial cells in both the CNS and the PNS. Most recently, a clinical trial has revealed the beneficial effects of IGF-I in amyotrophic lateral-sclerosis (ALS), a degenerative disease of the motoneurones. We review briefly here experimental and clinical information that suggests the potential usefulness of IGF-I in the treatment of certain neurodegenerative diseases, including ALS, Alzheimer's disease, various neuropathies and brain trauma. The rather unique propensity of IGF-I to act on a variety of neuronal cells might provide a general means of reducing or slowing down neuronal losses that occur following various brain insults.
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PMID:Rediscovering an old friend, IGF-I: potential use in the treatment of neurodegenerative diseases. 924 19

The albumin excretion rate (AER), insulin-like growth factor-I (IGF-I) levels, glomerular filtration rate (GFR) and glycosylated hemoglobin (HbA1c) levels were studied in 49 diabetic children and 49 controls. The duration of diabetes varied from newly diagnosed to 17.5 years. Diabetics exhibited a wide range of AER values and had significantly higher AER and IGF-I levels compared to controls. At puberty elevated circulating growth hormone (GH) concentrations were found with a parallel increase in the levels of IGF-I. High IGF-I levels were found in 10-12 year-old girls and 15-16 year-old boys in both diabetic and control groups. Positive correlations were found between IGF-I and GFR in girls of both groups (p < 0.05) and in control girls between IGF-I, GFR and microalbuminuria (p < 0.05). The diabetic boys also showed microalbuminuria with respect to controls at high HbA1c levels and when their testis volume exceeded 8 ml (p < 0.05). We concluded that the prominent change in GH release at puberty, reflected by IGF-I, is in pulse amplitude, and that this is increased in diabetes but it is not a very important factor when determining the abnormal levels of urinary albumin excretion.
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PMID:Albumin excretion rate, serum insulin-like growth factor-I and glomerular filtration rate in type I diabetes mellitus at puberty. 936 55

The difficulties of achieving good glycaemic control in insulin-dependent diabetes are due in large part to the inadequacies of subcutaneously administered insulin. In particular, resorption with the long acting form is variable from one subject to another and from one day to another and irregular over time, whereas the action of the rapid acting form is too late and prolonged. The slowness of absorption of the rapid acting form is attributable to the need for hexamer dissociation. The Lilly Laboratories, by inverting the amino acids lysine and proline in positions 28 and 29 in the B chain, have created an insulin (Lispro) which more rapidly dissociates into monomers after injection. The stability of Lispro is good, probably because of its phosphate buffer. In our experience, in conditions simulating use in portable insulin pumps, Lispro proved to be more stable than insulins specially intended for this use. The affinity in vitro was identical to that of insulin for its receptor. The affinity for insulin-like growth factor-I (IGF-I) receptor has been found to be 1.5 times as high as that of fast insulin in some models and comparable in others, and nearly 1,000 times less than that of IGF-1. Studies on in vivo potency and ex vivo cell growth, as well as of tolerance in the animal (mutagenicity, toxicity and carcinogenicity), have not shown a different effect from regular insulin (contrary to results for analogue Asp B10). The pharmacokinetics has shown an earlier and higher insulinaemic peak and a more rapid return to baseline values than regular insulin. On the basis of pharmacokinetic studies in normal subjects and diabetic patients, the characteristics retained by the licensing authorities are onset of action at 15 min, insulinemic peak between 30 and 70 min, and duration of action 2 to 5 h. Some clinical studies have shown a shortened action period of 1 to 3 h as compared to regular insulin and less influence of dose and injection site, notably with a return to normal insulin levels. The time required for normalisation is increased by 1 h if the injection is made in the thigh rather than the abdomen, as compared to 2 to 3 h for conventional insulin. This suggests that Lispro should be administered just before the meal (0 to 15 min). In some patients, an insulin with prolonged action can be added if the interval between injections is prolonged, i.e. always at the evening meal but possibly also at the noon meal. Lispro can be mixed with Umuline NPH or Umuline zinc without any alteration in its pharmacokinetics and potency if the injection is performed immediately. The few studies that have considered glycaemic stability and reproducibility have shown a tendency toward improvement in glycaemic excursions during the day, as measured by MAGE, and in insulinaemia variability expressed in area under the curve, which was reduced by half in the same individual or from one individual to another, with less marked impact on the variability from one day to another of glycaemic excursions. On the whole, Lispro provides faster kinetics, greater stability and possibly better reproducibility than fast insulin. These advantages, if confirmed by clinical experience, should allow an improvement in the comfort and glycaemic stability of diabetic patients.
Diabetes Metab 1997 Sep
PMID:[From the concept of fast acting analogs to the properties of the insulin Lispro]. 941 May 52

To investigate whether recombinant human insulin-like growth factor-I (rhIGF-I) has direct effects on the insulin requirement to maintain euglycemia independent of the growth hormone (GH) level, nine subjects with insulin-dependent diabetes mellitus ([IDDM] seven females; median (range) age, duration of diabetes, and hemoglobin A1C [HbA1C], 16.9 (12.5 to 21.9) years, 11.8 (4.6 to 16.8) years, and 9.8% (7.9% to 14.1%), respectively) underwent two euglycemic studies (6:00 PM to 8:00 AM) after double-blind subcutaneous administration of rhIGF-I/placebo (40 microg/kg). Octreotide infusion (300 ng/kg/h) suppressed endogenous GH, and three identical discrete GH pulses were infused on both nights. Variable-rate insulin infusion maintained euglycemia. Samples were taken every 15 minutes (glucose and GH), 30 minutes (insulin and intermediate metabolites), and 60 minutes (IGF-I and nonesterified fatty acids [NEFA]). Variables were analyzed during the steady-state period of euglycemia (4:00 to 8:00 AM). Data are expressed as the mean +/- SEM. The insulin infusion rate and free-insulin level were both significantly reduced after rhIGF-I administration (0.13 +/- 0.03 v placebo 0.23 +/- 0.05 mU/kg/min, P = .04, and 8.4 +/- 1.3 v placebo 12.1 +/- 1.4 mU/L, P = .03, respectively). GH pulse-related changes in the insulin requirement observed after placebo were not present after rhIGF-I. Glucagon levels were equally suppressed on both nights. Insulin clearance was not altered after rhIGF-I administration. NEFA and ketone levels also were not different on the 2 nights. In conclusion, in adolescents and young adults with diabetes, rhIGF-I administration directly affected insulin requirements independent of GH levels, but had no effect on fatty acid or ketone levels. This difference is related to the abolition of changes in the insulin requirement after GH pulses, and would suggest a complex interaction between GH and IGF-I on insulin action.
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PMID:Recombinant human insulin-like growth factor-I abolishes changes in insulin requirements consequent upon growth hormone pulsatility in young adults with type I diabetes mellitus. 944 Apr 74

This study found that early postnatal hypoglycaemia was mainly induced by foetal hyperinsulinaemia, in close relation to maternal hyperglycaemia, even in well-controlled pregnancies of 59 mothers with insulin-treated diabetes mellitus, 29 with insulin-dependent diabetes mellitus and 30 with gestational diabetes mellitus. Ten of the newborn children (17%) had a blood glucose concentration below 1.0 mmol l(-1) at 2 h postnatally. Cord insulin-like growth factor-I or glucagon concentrations were not related to the early decline of blood glucose.
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PMID:Early postnatal hypoglycaemia in newborn infants of diabetic mothers. 947 19

Insulin-like growth factor-I (IGF-I) is implicated in the development, survival and maintenance of function of sympathetic and sensory neurons. These neurons are affected at an early stage during the course of diabetes. Reverse transcriptase polymerase chain reaction (RT-PCR) based assay revealed that rat superior cervical ganglia (SCG) express mRNA transcripts for IGF-I and its receptor. Moreover, specific membrane protein binding sites for IGF-I within the SCG have also been demonstrated using competition-inhibition and affinity cross-linking techniques. An induction of diabetes with streptozotocin (STZ, 55 mg/kg, i.v.) produced a marked decrease in the SCG levels of mRNA transcripts for IGF-I and its receptor. Concentrations of circulating IGF-I and its receptor protein within the SCG were also reduced in this disease state. Insulin treatment partially prevented diabetes-related alterations in circulating IGF-I and the SCG-IGF-I system. Overall, the data described in this study may be of value in understanding the pathogenetic mechanism(s) responsible for the development of diabetic sympathetic neuropathy.
Diabetes Res Clin Pract 1997 Nov
PMID:Diabetes-induced suppression of IGF-1 and its receptor mRNA levels in rat superior cervical ganglia. 948 70

Diabetes in both humans and rats is accompanied by low bone formation, which is presumably caused by serum-borne factors. To explore its pathogenesis, we carried out experiments in diabetic and nondiabetic BB rats, using plasma osteocalcin concentrations (OC) as a marker for osteoblast activity. In nondiabetic rats, the i.v. infusion of glucose (30%, 4 d) did not change OC; s.c. insulin infusion (4 U/d, 14 d) reduced OC by 27% (p < 0.01). In diabetic rats, OC were decreased from the first day of glycosuria (71 +/- 5% of paired controls), declining exponentially to 24 +/- 3% after 5 wk. Insulin infusion (1, 2, and 3 U/d, 14 d) produced gradual restoration of OC. OC were better correlated with insulin-like growth factor-I (IGF-I) than with insulin levels in these experiments. OC were dramatically increased 4 d after adrenalectomy (ADX) in all diabetic rats (73 +/- 8 vs 22 +/- 4 micrograms/L before ADX; p < 0.001), but not if corticosterone was administered. Ligand blotting of IGF binding proteins showed a marked decrease in two bands (44-49 and 32-35 kDa) 10-14 d after diabetes onset; the density of these bands was increased, but not normalized after ADX. Thus, decreased osteoblast activity is present from the onset of diabetes, is dependent on endogenous corticosterone, and cannot be reproduced by hyperglycemia in nondiabetic rats.
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PMID:Decreased osteoblast activity in spontaneously diabetic rats. In vivo studies on the pathogenesis. 954 42


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