Understanding Oral Glucose Tolerance: Comparison of Glucose or Insulin Measurements During the Oral Glucose Tolerance Test with Specific Measurements of Insulin Resistance and Insulin Secretion

The extent to which the oral glucose tolerance test can be used to estimate insulin secretion and insulin resistance has been evaluated by comparing glucose and insulin concentrations during an oral glucose tolerance test with specific measurements of insulin secretion and insulin resistance in 85 normoglycaemic subjects and 23 subjects with impaired glucose tolerance (IGT). Insulin secretion was measured by the first phase insulin response to intravenous glucose and insulin resistance by the insulin tolerance test which measures the decline of plasma glucose after the injection of a bolus of insulin. The best measure of insulin secretion was the ratio of the 30 min increment in insulin concentration to the 30 min increment in glucose concentration following oral glucose loading. This correlated with the first phase insulin release following intravenous glucose (r=0.61, p < 0.001) but not insulin resistance (r= ?0.05, p >0.05). Insulin resistance could be estimated by the fasting insulin, proinsulin, or split proinsulin concentrations. However, fasting split proinsulin appeared to discriminate best between insulin resistance (r = ?0.53, p < 0.001) and insulin secretion (r = 0.07, p > 0.05). Relative insulin resistance estimated by homeostasis model assessment (HOMA) also correlated well with insulin resistance (r= ?0.57, p < 0.001) but not insulin secretion (r= 0.01, p > 0.05). We conclude that the oral glucose tolerance test can be used to derive estimates of the relative roles of insulin secretion and insulin resistance in population studies of glucose tolerance.     

高氟对机体内分泌激素水平的影响

目的探讨高氟状态对有关内分泌腺的影响及与激素水平的关系.方法采用流行病学的病例-对照研究方法,对实验动物昆明种小鼠及高氟区人群的血清垂体、甲状腺及性腺激素含量进行了测定,用以观察上述群体高氟与有关内分泌腺的关系. 结果随着染氟剂量的增加,实验仔鼠血清促甲状腺素(TSH)、甲状腺素(T4)、雌二醇(E2)含量呈剂量依赖性降低,高剂量组(500mg/L NaF)明显低于对照组(P<0.05).高氟区成年男性睾酮(T)含量显著降低(P<0.05),而垂体分泌的黄体生成素(LH)、卵泡刺激素(FSH)水平则升高(P<0.05);女性人群血清LH,FSH,E2,P含量均低于对照人群,而LH,E2水平则明显降低(P<0.05).结论高氟状态可干扰机体垂体、甲状腺、性腺等内分泌腺体的分泌功能;氟对机体内分泌功能的影响可以通过生殖过程传给子代,进而导致子代的损伤.     

Ghrelin Stimulation of Growth Hormone Isoforms: Parallel Secretion of Total and 20-kDa Growth Hormone and Relation to Insulin Sensitivity in Healthy Humans

Context: The 20-kDa human GH (hGH) is produced in the pituitary by alternative splicing of the hGH-N gene. The 20-kDa hGH promotes growth similarly to 22-kDa or total hGH, the predominant form in circulation, but the relative effects of these isoforms on glucose metabolism have been debated. Objective: To investigate the effect of ghrelin on 20-kDa and total hGH secretion in healthy, nonobese subjects. We also studied associations between basal GH concentration and fasting glucose and insulin as well as between dynamic GH secretion and insulin sensitivity. Design and Setting: Synthetic human acyl ghrelin (0.2 or 0.6 nmol/kg · h) or saline was infused in random order in 14 healthy subjects (six males, eight females; age 27.7 ± 6.3 yr; body mass index 22.0 ± 2.7 kg/m(2), mean ± sem) on 3 separate days. Ghrelin was infused for 45 min to achieve steady-state levels and continued through a 3-h frequently sampled iv glucose tolerance test. Insulin sensitivity index was quantified using the minimal model of glucose kinetics. Results: Basal 20-kDa and total GH concentrations were 0.4 ± 0.1 and 2.2 ± 0.4 ng/ml, respectively, with a 20-kDa to total GH ratio of 0.13 ± 0.02. Females had significantly higher baseline GH levels. Ghrelin administration increased 20-kDa and total GH levels in a parallel and dose-dependent fashion, with no significant change in the ratio of the isoforms. Basal 20-kDa and total GH levels were negatively correlated with fasting glucose, insulin, and homeostasis model assessment of insulin resistance. During the frequently sampled iv glucose tolerance test, GH secretion was positively correlated with insulin sensitivity index with saline infusion. Conclusion: Ghrelin dose-dependently increases endogenous 20-kDa and total GH secretion in a parallel fashion in healthy subjects. Both basal and stimulated levels of the different GH isoforms were positively associated with insulin sensitivity in this cohort of healthy men and women.     

Complex Rhythmicity of Growth Hormone Secretion in Humans

To better characterize the 24 hr GH secretion pattern in humans, we studied frequently sampled 24 hr GH profiles in 93 young (18–45 years of age) healthy, fed volunteers: men (n = 67) and women (n = 26) with BMI<26kg/m². Analysis of the composite GH series in men revealed 3 significant GH “waves” with peaks occurring at midnight (p < 0.0001), at noon (p < 0.02) and at 1800h (p < 0.0001). In women, similar pattern was seen, with three GH “waves” peaking at midnight (p < 0.0001), 1100h (p < 0.02) and at 1600h (p < 0.002). We conclude that the 24 hr rhythmicity of GH secretion is far more complex than currently appreciated. The attribution of the two daytime GH “waves” to food consumption is unlikely but cannot be excluded at the present time. The complex temporal pattern of pulsatile GH secretion may have important effects on regulation of target cell function.     

The Mechanism of Insulin Secretion after Oral Glucose Administration

Summary In conscious trained dogs (Alsatians) the IRI-concentration in the peripheral venous blood after oral administration of glucose increases when the blood glucose is still unchanged. After one or two peaks during the first 20 min IRI increases parallel to the blood sugar increase. In relation to the intravenous injection of glucose the IRI maximum after oral administration occurs earlier. Furthermore the ratio of the IRI to blood sugar areas is raised. Without any blood sugar change the IRI concentration after oral application of tap water increases with one or two peaks. These peaks correspond to the first peaks after oral administration of glucose. These findings are discussed in the sense of a feed-forward of insulin secretion after feeding via N.vagus as well as via enterohormones. More attention should be payed to the IRI course during the early phase of the oral glucose tolerance test.

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Der Mechanismus der Insulinmobilisierung nach oraler GlucosegabeI. Mehrphasigkeit der Insulinmobilisierung nach oraler Glucosegabe beim wachen Hund und Differenzen zum Verhalten nach intravenöser Glucoseinjektion

Zusammenfassung Bei wachen trainierten Schäferhunden steigt die Insulinkonzentration im peripheren Venenblut nach oraler Glucosegabe schon zu einem Zeitpunkt an, da die Glykämie noch nicht verändert ist. Nach Durchlaufen von 1 oder 2 Gipfeln in den ersten 20 min tritt der Anstieg ein, der parallel dem Blutzuckergipfel verläuft. Im Verhältnis zur intravenösen Glucosegabe liegt das erste IRI-Maximum nach oraler Verabfolgung zeitlich früher. Auch ist der Quotient aus IRIÜberschreitungsfläche und Blutzuckerüberschreitungsfläche erhöht. Ohne daß es zu einer Blutzucker Veränderung kommt, steigt auch nach oraler Gabe von Leitungswasser die IRI-Konzentration 1-oder 2gipflig an. Diese Gipfel entsprechen den beiden ersten Erhöhungen nach oraler Glucosegabe. Die beobachteten Phänomene werden im Sinne einer Vorwärtskopplung der Insulinsekretion nach Nahrungsaufnahme via N.vagus und Enterohormone diskutiert. Der Beurteilung des IRI-Verlaufs in der frühen Phase des oralen Glucosetoleranztests sollte größere Beachtung geschenkt werden.

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Mécanisme de la sécrétion d'insuline après administration orale de glucoseI. Déroulement multiphasique de la mobilisation de l'insuline après administration orale de glucose chez le chien éveillé. Différences de comportement après administration intraveineuse

Résumé Chez des chiens-bergers éveillés et entraînés, après administration orale de glucose, la concentration d'IRI dans le sang veineux périphérique augmente déjà alors que la glycémie n'a pas encore changé. Après un ou deux pics durant les vingt premières minutes, l'IRI augmente parallèlement au glucose sanguin. Comparativement à l'injection intra-veineuse de glucose, le maximum d'IRI, après administration orale, se produit plus tôt. De plus, le quotient des surfaces d'IRI et de glycémie est élevé. Sans aucun changement du glucose sanguin, la concentration d'IRI augmente avec un ou deux pics après administration orale d'eau potable. Ces pics correspondent aux deux premiers pics après administration orale de glucose. Ces résultats sont discutés dans le sens d'une sécrétion d'insuline précédant la digestion via N.vague et via entérohormones. Il faut accorder plus d'attention à l'évolution d'IRI durant la première phase du test de tolérance au glucose par voie orale.

     

Normal Growth Hormone Secretion is Rare after Microsurgical Normalization of Growth Hormone Levels in Acromegaly

ABSTRACT. The effect of microsurgery on growth hormone (GH) secretion was studied in 34 patients with acromegaly. All patients showed enlarged sella volumes according to encephalography and macro-adenomas at surgery. Preoperative GH levels were elevated in all 34 patients and 14 had concomitant hyperprolactinemia. There was a correlation between basal GH levels and sella size. Visual field defects, suprasellar extension, long duration of the disease, hyperprolactinemia and aneuploidy were noted in patients with low as well as high levels of GH pre-operatively. The average reduction of GH levels in the total series was 71 ± 21% (mean ± SD). A notably similar reduction of GH levels was seen regardless of preoperative GH levels, concomitant hyperprolactinemia, visual field defects, size of the adenoma, invasive growth or increasing experience of the surgeon. Therefore, normal GH levels after surgery were reached mainly in patients with moderate GH increments preoperatively. GH levels were normalized by surgery in 15 patients but only four of these showed normal GH response to TRH and l-dopa tests. Thus, only four patients (12%) fulfilled these criteria for cure of GH homeostasis.     

Effect of Ethanol on Endogenous Rhythms of Growth Hormone Secretion

Studies in man on the effect of ethanol on growth hormone (GH) release have been inconclusive. In order to investigate the effect of ethanol on spontaneous episodic secretion of GH, rats were implanted with chronic carotid catheters to permit frequent sampling in unanesthetized rats. Secretion during the 3 hr before (0–180 min) and after (181–360 min) ethanol or saline was assessed by means of samples drawn every 15 min. Secretion patterns after saline or ethanol 0.5 and 2 g/kg were indistinguishable, but ethanol in doses of 3 and 4 g/kg abolished rat GH (rGH) secretion in a majority of animals. Mean rGH after saline injection for the period 181–360 min was 62 ± 9 ng/ml. When ethanol was given, mean rGH values for this time period were 0.5 g/kg, 63 ± 6 ng/ml; 2.0 g/kg, 47 ± 7 ng/ml; 3 g/kg. 28 ± 3 ng/ml; and 4 g/kg, 23 ± 2 ng/ml. Differences were not statistically significant between saline and 0.5 or 2 g/kg ethanol, but were significant (p < 0.01) for 3 or 4 g/kg ethanol. Thus, a single dose of ethanol can abolish spontaneous rGH secretion, but it must be a high dose. The effect of chronic ethanol administration remains to be investigated.     

Effects of Branched-Chain-Enriched Amino Acid Solution on Insulin and Glucagon Secretion and Blood Glucose Level in Liver Cirrhosis

Background: The aim of this study was to determine whether therapeutically used branched-chain amino acids (BCAAs) solution influences glucose metabolism in liver cirrhosis (LC). Methods: BCAAs solution (200 ml) was infused in LC patients at different stages, and plasma concentrations of glucose and pancreatic hormones were determined. Results     

Melatonin Effects on Prolactin Secretion in Pituitary-Grafted Male Rats

Melatonin influences prolactin (PRL) secretion through unknown mechanisms. This work was undertaken to study the effects of melatonin administration on PRL secretion in pituitary-grafted male rats. Melatonin administration 5 hours before dark resulted in a marked decrease of previously high basal plasma PRL levels in pituitary-grafted rats, whereas a marked increase was detected in sham-operated animals. Vehicle treatment did not modify basal PRL values in grafted or sham-operated animals. Luteinizing hormone-releasing hormone (LHRH) administration resulted in a marked decrease of plasma PRL levels in vehicle-treated, sham-operated or grafted rats, as well as in melatonin-treated sham-operated rats. An increase in PRL levels was shown in grafted rats treated with melatonin. Estradiol benzoate (EB) administration resulted in an increase in plasma PRL levels both in sham-operated and grafted vehicle-treated rats. No PRL response could be detected in sham-operated, melatonin-treated animals after EB administration. In pituitary-grafted animals given melatonin, PRL response to EB administration was slight and delayed. From these data, melatonin appears to modify PRL secretion through multiple complex mechanisms that may depend on the physiological status (hormonal and neurotransmitter) of the animals. A direct effect at the pituitary level altering lactotroph sensitivity seems to be one plausible explanation for the current findings, although an hypothalamic site of action cannot be excluded.     

Reduced Insulin Secretion by Subtotal Pancreatectomy: Preservation of Insulin Sensitivity and Glucose Tolerance in Postoperative Patients

This study investigated insulin sensitivity and glucose tolerance after subtotal pancreatectomy for carcinoma of the head of the pancreas. Twelve consecutive, non-diabetic patients were studied after potentially curative surgery at which the distal pancreas was stapled off, leaving approximately 15% of the pancreas in situ. Brief infusions of insulin (10mUkg-1) and glucose (25 g) were given before and 4 days after operation. Postoperatively, blood glucose levels remained unchanged, whereas fasting levels of insulin, C-peptide, and pancreatic glucagon were decreased, although significantly (p < 0.01) only for glucagon. The early and late phases of the insulin and C-peptide responses to glucose were severely reduced. Notably, the hypoglycemic action of insulin and the glucose tolerance were similar to those observed before operation. It is concluded that an acute reduction in pancreatic mass does not impair insulin action or glucose tolerance shortly after surgery. This contrasts with the insulin resistance and glucose intolerance seen shortly after pancreas-preserving intra-abdominal procedures of similar size. It is suggested that the decrease in glucagon levels is at least partly responsible for the preservation of insulin action after subtotal pancreatectomy.     

Transient Suppression of Growth Hormone Secretion after Chronic Ethanol Intake

Fifty-two percent of patients with chronic heavy intake of ethanol had an abnormally low growth hormone (GH) response to propranolo-glucagon. The effect of ethanol is transient, since the GH response was normal in patients studied 2 wk or more after withdrawal of ethanol. The low GH response was not due to a difference in the levels of glucose or insulin. Ethanol probably suppresses the GH response by acting on the hypothalamus or pituitary gland. Along with previous data suggesting transient ACTH deficiency in chronic alcoholic patients, our findings suggest that these patients may have multiple hypothalamic-pituitary deficiencies.     

Gastric Acid Secretion and Changes in Blood Glucose after Insulin in Another Healthy Man

Eight studies of gastric acid secretion in a basal hour and after a single intravenous injection of soluble insulin (0.003–0.4 units/kg) were performed in a healthy man. The peak acid output after insulin was significantly correlated with the lowest concentrations of blood glucose and the maximum fall in blood glucose. Peak acid output increased linearly with log dose of insulin up to a dose of 0.05 units/kg, and higher doses evoked a smaller response. Insulin-stimulated acid secretion is dose-dependent, although the dose of insulin which produces the greatest acid output varies between individuals. Insulin hypoglycaemia produces a quantitative vagal acid response, a blood glucose of about 25 mg/100 ml is associated with the greatest acid stimulation, and blood glucose concentration below 15 mg/100 ml is associated with inhibition of acid secretion.     

The Effects of Naloxone and Morphine on Postprandial Gastrointestinal Hormone Secretion

Postprandial gastrointestinal hormone secretion was not affected by the intravenous administration of naloxone. However, after the administration of morphine, multiple effects were observed. Postprandial pancreatic polypeptide, motilin, and enteroglucagon secretion were abolished and there was a reduction in the secretion of insulin, gastric inhibitory polypeptide, and neurotensin. There was prolonged secretion of gastrin. Levels of vasoactive intestinal polypeptide, somatostatin, and pancreatic glucagon were not affected. Many of these changes can be accounted for by the ability of morphine to delay gastric emptying. The prolonged secretion of gastrin could result from a combination of impaired gastric emptying and reduced postprandial gastric acid secretion. Inhibition of vagal acetylcholine release is the most likely explanation for the abolition of pancreatic polypeptide secretion. With the exception of the effects on motilin, pancreatic polypeptide, and enteroglucagon secretion this study provides no evidence that opiate substances directly affect the secretion of gastrointestinal hormones.     

Changes in Blood Glucose and Insulin Secretion in Patients with Senile Dementia of Alzheimer Type

ABSTRACT A retrospective study of 839 hospital records with various dementia diagnoses showed that 63 cases had a diagnosis of diabetes mellitus as well. None of these were found in the group of patients with senile dementia of Alzheimer type (SDAT). Oral glucose tolerance tests (OGTT) were performed in patients with SDAT, multiinfarct dementia (MID), cerebrovascular disease (CVD), hospitalized control patients (C_hosp) and healthy elderly persons (C_eld). Fasting blood sugar was significantly lower and the areas under the OGTT curves were significantly smaller in the SDAT group than in the CVD and the C_hosp group. SDAT patients had higher insulin levels than C_eld during the OGTT and on a statistically significant level 90 min after ingestion of sugar. Our findings suggest that SDAT and diabetes mellitus may not co-exist and that patients with SDAT have decreased blood sugar concentrations and elevated serum insulin levels. It is discussed whether this is an effect of the transmitter deficiencies in SDAT or may serve to explain these deficiencies.     

The Impact of a Family History of Type 2 Diabetes on Insulin Secretion and Insulin Sensitivity in Individuals With Varying Glucose Tolerance

IntroductionThis study was performed to investigate the impact of a family history of type 2 diabetes (T2DM) on insulin resistance and beta-cell dysfunction in populations with varying glucose tolerance.MethodsAmong the total of 142 participants, 73 subjects with no family history of T2DM (FH?) included 42 with normal glucose tolerance (NGT/FH?) and 31 with impaired glucose tolerance (IGT/FH?); and 69 first-degree relatives of patients with T2DM (FH+) included 36 with NGT (NGT/FH+) and 33 with IGT (IGT/FH+). Insulin resistance was evaluated by Insulin Sensitivity Index (ISI) based on the euglycemic hyperinsulinemic clamp. Islet beta-cell function was assessed by disposition index (DI) for the acute insulin response to glucose (AIRg) using intravenous glucose tolerance test. Metabolic data were compared between groups after adjustment for age, sex, body mass index and waist-to-hip ratio.ResultsThe NGT/FH+ group showed lower level of ISI (P = 0.023) than the NGT/FH? group, whereas no difference was found in AIRg or DI between these 2 subgroups. In the FH? individuals, both ISI and DI of the IGT/FH? group decreased compared with the NGT/FH? group (both P < 0.05). In the FH+ individuals, no difference was found in ISI between the IGT/FH+ and NGT/FH+ groups, whereas the IGT/FH+ group had a lower level of AIRg and DI than the NGT/FH+ group (both P < 0.0001).ConclusionsThis study showed that the pathophysiological changes were different between individuals with and without a family history of T2DM during the glucose tolerance aggravation.     

大脑葡萄糖感受器对于胰岛葡萄糖刺激的胰岛素分泌起显著调节作用

当患者从健康状态到罹患T2DM时,葡萄糖刺激的胰岛素分泌(GSIS)明显受损。尽管GISS主要是由胰岛β细胞对于血糖升高的直接感受所驱动,但有越来越多的证据表明,下丘脑神经元控制着外周葡萄糖代谢的其他方面。本文作者对大脑在GSIS的调节作用进行了研究。为了考察下丘脑葡萄糖感应增强或减弱对于葡萄糖耐量和胰岛素分泌     

Ethanol Has Direct Effects on Human Choriocarcinoma Cell Steroid Hormone Secretion

Clinical observations indicate that ethanol (EtOH) consumption has significant detrimental effects on pregnancy. However, there is a paucity of information on effects of EtOH on human placental function. We have used JEG choriocarcinoma cells that have many of the functional capabilities of syncytiotrophoblasts, as a model to study direct effects of EtOH on placental function. Between 20–100 mM EtOH decreased rate of cell growth by 25%, but no decrease in [³⁵S]methionine incorporation into protein was noted. EtOH decreased in a dose-dependent manner the secretion of progesterone (P₄) in response to cAMP when added with cAMP or when cells were pretreated with EtOH for 2 days. But after 4 or 6 days of pretreatment with EtOH, the P₄ response to cAMP was increased by EtOH. Furthermore, EtOH increased the stimulation of P₄ secretion by Forskolin. The development of this response was dependent on the period of exposure to EtOH. EtOH also increased estradiol (E₂) secretion by unstimulated JEG cells in a dose- and time-dependent manner and increased cAMP stimulated E₂ secretion >2-fold following 4 days of pretreatment with EtOH. These results suggest that EtOH may directly alter hormone secretion by placental cells and such perturbations of endocrine function of the placenta may be responsible for some of the effects of EtOH on pregnancy.