First-phase insulin secretion is positively correlated with alanine aminotransferase in young adults

Abstract. The ability of the cholinergic agonist carbachol to sensitize islets to the action of combined glucose, cholecystokinin and gastric inhibitory polypeptide was determined in isolated rat islets. In response to this combination, peak first phase insulin secretion from control islets averages 85 ± 5 pg · islet−1 · min−1 (mean ± sem) and the insulin secretory rates measured 35–40 min after the onset of stimulation averages 127 ± 34 pg · islet−1 · min−1. A prior 20 min exposure to 1 mmol/l carbachol potentiates the modest insulin stimulatory response to this combination of stimulants: peak first phase release is 354 ± 61 pg · islet−1 · min−1, and release measured 35–40 min after the onset of stimulation is 179 ± 34 pg · islet−1 · min−1. This sensitizing effect of carbachol lasts for at least 40 min and can be duplicated by the natural in vivo agonist acetylcholine. These results demonstrate that cholinergic stimulation of isolated islets primes them to the subsequent stimulatory effect of a moderate increase in the circulating glucose level and to several postulated incretin factors. If operative in vivo, this communications network between cephalic and enteric factors represents a remarkable control system to ensure the release of insulin in amounts commensurate to meet the anticipated and actual insulin requirements for insulin-mediated fuel disposition.

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Effects of maternal periconceptional undernutrition in sheep on offspring glucose–insulin axis function into adulthood

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174420001063 ◽

2020 ◽

pp. 1-7

Author(s):

Mark H. Oliver ◽

Frank H. Bloomfield ◽

Amita Bansal ◽

Hui Hui Phua ◽

Eric B. Thorstensen ◽

...

Keyword(s):

Insulin Secretion ◽

Glucose Tolerance ◽

Protein Expression ◽

Insulin Signalling ◽

Area Under The Curve ◽

Late Gestation ◽

Maternal Undernutrition ◽

Kinase C ◽

First Phase Insulin Secretion ◽

Protein Kinase C Zeta

Abstract Maternal periconceptional undernutrition (PCUN) affected fetal pancreatic maturation in late gestation lambs and impaired glucose tolerance in 10-month-old sheep. To examine the importance of the timing of maternal undernutrition around conception, a further cohort was born to PCUN ewes [undernourished for 61 d before conception (PreC), 30 d after conception (PostC), or 61 d before until 30 d after conception (PrePostC)], or normally fed ewes (Control) (n = 15–20/group). We compared glucose tolerance, insulin secretion, and sensitivity at 36 months of age. We also examined protein expression of insulin signalling proteins in muscle from these animals and in muscle from a fetal cohort (132 d of gestation; n = 7–10/group). Adult PostC and PrePostC sheep had higher glucose area under the curve than Controls (P = 0.07 and P = 0.02, respectively), whereas PreC sheep were similar to Controls (P = 0.97). PostC and PrePostC had reduced first-phase insulin secretion compared with Control (P = 0.03 and P = 0.02, respectively). PreC was similar to Control (P = 0.12). Skeletal muscle SLC2A4 protein expression in PostC and PrePostC was increased 19%–58% in fetuses (P = 0.004), but decreased 39%–43% in adult sheep (P = 0.003) compared with Controls. Consistent with this, protein kinase C zeta (PKCζ) protein expression tended to be increased in fetal (P = 0.09) and reduced in adult (P = 0.07) offspring of all PCUN ewes compared with Controls. Maternal PCUN alters several aspects of offspring glucose homeostasis into adulthood. These findings suggest that maternal periconceptional nutrition has a lasting impact on metabolic homeostasis of the offspring.

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Magnesium requirement for somatostatin inhibition of insulin secretion

Acta Endocrinologica ◽

10.1530/acta.0.1050083 ◽

1984 ◽

Vol 105 (1) ◽

pp. 83-86 ◽

Cited By ~ 2

Author(s):

Donald L. Curry ◽

Leslie L. Bennett

Keyword(s):

Insulin Secretion ◽

Calcium Concentration ◽

Inhibitory Effect ◽

Secretory Process ◽

Magnesium Ion ◽

Second Phase ◽

Intracellular Membrane ◽

Calcium Magnesium ◽

First Phase Insulin Secretion ◽

Insulin Secretory Response

Abstract. Rat pancreas perfusions were performed using a perfusate with a fixed calcium concentration of 5 mEq/l and magnesium varying from 0 to 0.6 mEq/dl. Insulin secretion was stimulated by a constant glucose infusion of 300 mg/dl. This glucose concentration produces the typical biphasic insulin secretory response. We observed that in the absence of magnesium, somatostatin concentrations of 0.5 and 2.0 ng/ml were without effect on first phase insulin secretion. However, these same somatostatin levels produced 50% or more inhibition of insulin secretion in the presence of magnesium at 0.3 or 0.6 mEq/l. Similarly, in the absence of magnesium, somatostatin at 50 ng/ml failed to inhibit second phase insulin secretion, whereas this same somatostatin level produced about 50% inhibition of insulin secretion in the presence of magnesium at 0.3 mEq/l. Thus, altering perfusate magnesium concentrations without changing calcium is an important determinant of the degree of inhibition of secretion produced by somatostatin. In particular, in the absence of magnesium ion, somatostatin concentrations which would 'normally' produce 50% inhibition of secretion (ID50) are without effect. Therefore, magnesium ion is necessary for the full inhibitory effect of somatostatin to occur. These results suggest that inhibitors, as well as potentiators, of the insulin secretory process may act by altering intracellular/membrane calcium-magnesium ratios, but in opposite directions.

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Study of Glucose Removal Rate and First Phase Insulin Secretion in the Offspring of Two Parents with Non-Insulin-Dependent Diabetes

Prediabetes - Advances in Experimental Medicine and Biology ◽

10.1007/978-1-4684-5616-5_21 ◽

1988 ◽

pp. 175-183 ◽

Cited By ~ 7

Author(s):

James H. Warram ◽

Blaise C. Martin ◽

J. Stuart Soeldner ◽

Andrzej S. Krolewski

Keyword(s):

Insulin Secretion ◽

Removal Rate ◽

Insulin Dependent Diabetes ◽

Insulin Dependent ◽

First Phase Insulin Secretion

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Overnight inhibition of insulin secretion restores pulsatility and proinsulin/insulin ratio in type 2 diabetes

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.2000.279.3.e520 ◽

2000 ◽

Vol 279 (3) ◽

pp. E520-E528 ◽

Cited By ~ 71

Author(s):

Thomas Laedtke ◽

Lise Kjems ◽

Niels Pørksen ◽

Ole Schmitz ◽

Johannes Veldhuis ◽

...

Keyword(s):

Type 2 Diabetes ◽

Insulin Secretion ◽

Plasma Glucose ◽

Glucose Concentration ◽

Plasma Glucose Concentration ◽

Molar Ratio ◽

Β Cell ◽

First Phase Insulin Secretion ◽

Clinical Experiments

Impaired insulin secretion in type 2 diabetes is characterized by decreased first-phase insulin secretion, an increased proinsulin-to-insulin molar ratio in plasma, abnormal pulsatile insulin release, and heightened disorderliness of insulin concentration profiles. In the present study, we tested the hypothesis that these abnormalities are at least partly reversed by a period of overnight suspension of β-cell secretory activity achieved by somatostatin infusion. Eleven patients with type 2 diabetes were studied twice after a randomly ordered overnight infusion of either somatostatin or saline with the plasma glucose concentration clamped at ∼8 mmol/l. Controls were studied twice after overnight saline infusions and then at a plasma glucose concentration of either 4 or 8 mmol/l. We report that in patients with type 2 diabetes, 1) as in nondiabetic humans, insulin is secreted in discrete insulin secretory bursts; 2) the frequency of pulsatile insulin secretion is normal; 3) the insulin pulse mass is diminished, leading to decreased insulin secretion, but this defect can be overcome acutely by β-cell rest with somatostatin; 4) the reported loss of orderliness of insulin secretion, attenuated first-phase insulin secretion, and elevated proinsulin-to-insulin molar ratio also respond favorably to overnight inhibition by somatostatin. The results of these clinical experiments suggest the conclusion that multiple parameters of abnormal insulin secretion in patients with type 2 diabetes mechanistically reflect cellular depletion of immediately secretable insulin that can be overcome by β-cell rest.

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The effects of ethanol (0.75 g/kg body weight) on the activities of selected enzymes in sera of healthy young adults: 1. Intermediate-term effects.

Clinical Chemistry ◽

10.1093/clinchem/23.5.830 ◽

1977 ◽

Vol 23 (5) ◽

pp. 830-834 ◽

Cited By ~ 26

Author(s):

D E Freer ◽

B E Statland

Keyword(s):

Young Adults ◽

Body Weight ◽

Enzyme Activity ◽

Aspartate Aminotransferase ◽

Alanine Aminotransferase ◽

Ethanol Ingestion ◽

Similar Time ◽

Gamma Glutamyltransferase ◽

Time Courses ◽

Apparently Healthy

Abstract We report the intermediate-term effects of three consecutive evenings of moderate ethanol ingestion (0.75 g/kg body weight each evening) on activity values for alkaline phosphatase, gamma-glutamyltransferase, creatine kinase, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase in sera of nine apparently healthy young adults. We define "intermediate-term" effects as those occurring between 10 h and 100 h after completion of the ethanol consumption schedule. The most pronounced changes in enzyme activity for the group of volunteers were: gamma-glutamyltransferase, +25% at 60 h after ethanol ingestion; alanine aminotransferase, +12% at 60 h after ethanol; and aspartate aminotransferase,--12% at 60 h after ethanol. All three enzymes exhibited similar time courses, i.e., mean peak activity changes were observed at 60 h, and all three mean enzyme activity values returned to near baseline by 100 h. The possible explanations for the observed changes and the clinical significance are discussed.

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