Matched rates of insulin infusion and secretion and concurrent tracer-determined rates of glucose appearance and disappearance in fasting dogs

1968 ◽  
Vol 46 (3) ◽  
pp. 383-390 ◽  
Author(s):  
M. Vranic ◽  
G. A. Wrenshall
Keyword(s):  
Steady State ◽  
Insulin Infusion ◽  
Feedback Mechanism ◽  
Negative Feedback Mechanism ◽  
Glucose Levels ◽  
Normal Glucose ◽  
Graft Removal ◽  
Glucose Accumulation ◽  
Hypoglycemic Action ◽  
Diabetic Dog

The endogenous secretion rate of insulin in the dog was matched by an intraportal infusion of exogenous pork insulin at a rate of 12 milliunits/kg h following removal of the remnant pancreatic autograft. Both homeostasis and a dynamic steady state for glucose were observed. An apparent functional relationship between the infusion rates of insulin (7.2–16.4 milliunits/kg h) and the tracer-determined rates of glucose appearance and disappearance was found following graft removal, but not in the diabetic dog after reduction of hyperglycemia. With rates of insulin infusion less than 12 milliunits/kg h the rate of glucose appearance increased and the rate of its disappearance decreased, causing glucose accumulation. Opposite changes were observed with insulin infusion rates from 15 to 156 milliunits/kg h. When the infusion was switched from the portal to a nonsplanchnic vein the dog was more sensitive to the hypoglycemic action of insulin. The switch-off of insulin infusions, maintained for 4.5–7.0 h in the depancreatized dog at different glucose levels, resulted within 2 min in a rise in plasma glucose concentration caused by both underutilization and overproduction of glucose. Overproduction of glucose was still observed 15 h thereafter, when a new steady state was being approached. It is postulated that in the fasting dog at normal glucose levels a continuous insulin secretion of 12 milliunits/kg h is indispensable for the apparent negative feedback mechanism to maintain glucose near the dynamic steady state. In the absence of insulin, the apparent feedback mechanism becomes functional again but at high glucose levels.

scholarly journals NMR Determination of Intracerebral Glucose Concentration and Transport Kinetics in Rat Brain

1992 ◽  
Vol 12 (3) ◽  
pp. 448-455 ◽  
Author(s):  
Graeme F. Mason ◽  
Kevin L. Behar ◽  
Douglas L. Rothman ◽  
Robert G. Shulman
Keyword(s):  
Steady State ◽  
Plasma Glucose ◽  
Glucose Concentration ◽  
Goodness Of Fit ◽  
Glucose Consumption ◽  
Plasma Glucose Concentration ◽  
Transport Parameters ◽  
Glucose Levels ◽  
Normal Glucose ◽  
Wet Weight

The concentration of intracerebral glucose as a function of plasma glucose concentration was measured in rats by 13C NMR spectroscopy. Measurements were made in 20–60 min periods during the infusion of [1-13C]d-glucose, when intracerebral and plasma glucose levels were at steady state. Intracerebral glucose was found to vary from 0.7 to 19 μmol g−1 wet weight as the steady-state plasma glucose concentration was varied from 3 to 62 m M. A symmetric Michaelis–Menten model was fit to the brain and plasma glucose data with and without an unsaturable component, yielding the transport parameters Km, Vmax, and Kd. If it is assumed that all transport is saturable ( Kd = 0), then Km = 13.9 ± 2.7 m M and Vmax/ Vgly = 5.8 ± 0.8, where Vgly is the rate of brain glucose consumption. If an unsaturable component of transport is included, the transport parameters are Km = 9.2 ± 4.7 m M, Vmax/ Vgly = 5.3 ± 1.5, and Kd/ Vgly = 0.0088 ± 0.0075 ml μmol−1. It was not possible to distinguish between the cases of Kd = 0 and Kd > 0, because the goodness of fit was similar for both. However, the results in both cases indicate that the unidirectional rate of glucose influx exceeds the glycolytic rate in the basal state by 2.4-fold and as a result should not be rate limiting for normal glucose utilization.

scholarly journals Kinetic Model of Translational Autoregulation

2018 ◽  
Author(s):  
Vivian Tyng ◽  
Michael E. Kellman
Keyword(s):  
Steady State ◽  
Phase Space ◽  
Kinetic Model ◽  
Molecular Biology ◽  
Messenger Rna ◽  
Linear Models ◽  
Feedback Mechanism ◽  
Negative Feedback Mechanism ◽  
Feedback Set ◽  
System Phase

AbstractWe investigate dynamics of a kinetic model of inhibitory autoregulation as exemplified when a protein inhibits its own production by interfering with its messenger RNA, known in molecular biology as translational autoregulation. We first show how linear models without feedback set the stage with a nonequilibrium steady state that constitutes the target of the regulation. However, regulation in the simple linear model is far from optimal. The negative feedback mechanism whereby the protein “jams” the mRNA greatly enhances the effectiveness of the control, with response to perturbation that is targeted, rapid, and metabolically efficient. Understanding the full dynamics of the system phase space is essential to understanding the autoregulation process.

Ultrastructural morphology of nontumorous lactotrophs in human pituitaries exposed to high prolactin levels

1987 ◽  
Vol 45 ◽  
pp. 896-897
Author(s):  
S. Jalalah ◽  
K. Kovacs ◽  
E. Horvath
Keyword(s):  
Anterior Pituitary ◽  
Secretory Activity ◽  
Pituitary Hormones ◽  
Feedback Mechanism ◽  
Endocrine Activity ◽  
Hormone Synthesis ◽  
Anterior Pituitary Hormones ◽  
Negative Feedback Mechanism ◽  
Ultrastructural Morphology ◽  
Transmission Electron

Lactotrophs, as many other endocrine cells, change their morphology in response to factors influencing their secretory activity. Secretion of prolactin (PRL) from lactotrophs, like that of other anterior pituitary hormones, is under the control of the hypothalamus. Unlike most anterior pituitary hormones, PRL has no apparent target gland which could modulate the endocrine activity of lactotrophs. It is generally agreed that PRL regulates its own release from lactotrophs via the short loop negative feedback mechanism exerted at the level of the hypothalamus or the pituitary. Accordingly, ultrastructural morphology of lactotrophs is not constant; it is changing in response to high PRL levels showing signs of suppressed hormone synthesis and secretion.By transmission electron microscopy and morphometry, we have studied the morphology of lactotrophs in nontumorous (NT) portions of 7 human pituitaries containing PRL-secreting adenoma; these lactotrophs were exposed to abnormally high PRL levels.

STUDIES IN CONGENITAL GENERALIZED LIPODYSTROPHY (SEIP-BERARDINELLI SYNDROME)

1973 ◽  
Vol 72 (3) ◽  
pp. 475-494 ◽  
Author(s):  
Svein Oseid
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Normal Glucose Tolerance ◽  
Juvenile Form ◽  
Congenital Generalized Lipodystrophy ◽  
Glucose Levels ◽  
Normal Glucose ◽  
Glucose Tolerance Tests ◽  
The One ◽  
Adipose Organ

ABSTRACT Six cases of congenital generalized lipodystrophy have been studied at different ages from infancy to adolescence with regard to glucose tolerance, insulin secretion, and insulin sensitivity. During the first few years of life there is normal glucose tolerance. The fasting immuno-reactive insulin (IRI) levels are either slightly elevated or normal. The IRI response to glucose is exaggerated and prolonged, at least from the third year of life. Some degree of insulin resistance is already present in infancy. From the age of 8–10 years glucose tolerance decreases rapidly. The fasting IRI levels are usually grossly elevated, while fasting plasma glucose levels are only moderately elevated or normal. The IRI responses to oral and iv administered glucose, and to tolbutamide are exaggerated; the insulinogenic indices are high. Cortisone primed glucose tolerance tests become abnormal. Insulin resistance is marked, and increases with age. After cessation of growth at approximately 12 years of age, frank diabetes with fasting hyperglycaemia and diabetic glucose tolerance curves developed in the one patient followed beyond this age. Her fasting IRI was increased, but there was a poor IRI response to glucose stimulation, suggesting a partial exhaustion of the β-cells. Her initial IRI response to tolbutamide was still good, but not as brisk as in the younger patients. This type of diabetes is quite different from the juvenile form, and also from the diabetes of older age. It may be causally related to the lack of an adequate adipose organ necessary for the disposal of excesses of glucose, or possibly related to another anti-insulin mechanism.

Counterregulation of insulin-induced hypoglycaemia in primary hypothyroidism

1986 ◽  
Vol 111 (4) ◽  
pp. 516-521
Author(s):  
Nina Clausen ◽  
Per-Eric Lins ◽  
Ulf Adamson ◽  
Bertil Hamberger ◽  
Suad Efendić
Keyword(s):  
Growth Hormone ◽  
Insulin Infusion ◽  
Primary Hypothyroidism ◽  
Constant Rate Infusion ◽  
Counterregulatory Hormones ◽  
Insulin Metabolism ◽  
Hormonal Responses ◽  
Glucose Levels ◽  
Constant Rate ◽  
Rate Infusion

Abstract. Hypothyroidism has been alleged to modulate insulin action and influence the secretion of growth hormone and catecholamines. We recently investigated the influence of hypothyroidism on glucose counterregulatory capacity and the hormonal responses to insulin-induced hypoglycaemia in 6 patients with primary hypothyroidism (age 32–52 years, TSH-values 66–200 mU/l). Hypoglycaemia was induced in the hypothyroid state and again when the subjects were euthyroid. After an overnight fast a constant rate infusion of insulin (2.4 U/h) was given for 4 h. Glucose was measured every 15 min and insulin, C-peptide, glucagon, epinephrine, norepinephrine, growth hormone and cortisol every 30 min for 5 h. During insulin infusion somewhat higher concentrations of the hormone were obtained in the hypothyroid state and simultaneously glucose levels were 0.5 mmol/l lower. As expected, basal norepinephrine levels were higher in hypothyroidism. However, no increase in circulating norepinephrine during hypoglycaemia was registered in the two experiments. The responses of counterregulatory hormones showed an enhanced response of cortisol, similar responses of growth hormone and epinephrine while the glucagon response was paradoxically impaired. Our findings suggest that hypothyroidism alters insulin metabolism, and that the glucagon response to hypoglycaemia is impaired in this condition.

Effect of High ß-Glucan Barley on Postprandial Plasma Glucose Levels in Subjects with Normal Glucose Tolerance and Patients with Type 2 Diabetes

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 772-P
Author(s):  
MARIKO HIGA ◽  
AYANA HASHIMOTO ◽  
MOE HAYASAKA ◽  
MAI HIJIKATA ◽  
AYAMI UEDA ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Tolerance ◽  
Plasma Glucose ◽  
Normal Glucose Tolerance ◽  
Postprandial Plasma Glucose ◽  
Glucose Levels ◽  
Normal Glucose

scholarly journals Regulation of Store-Operated Ca2+ Entry by SARAF

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1887
Author(s):  
Inbal Dagan ◽  
Raz Palty
Keyword(s):  
Molecular Mechanisms ◽  
Feedback Mechanism ◽  
Cellular Biology ◽  
Excitable Cells ◽  
Major Pathway ◽  
Negative Feedback Mechanism ◽  
Crac Channels ◽  
Dependent Inactivation ◽  
Crac Channel ◽  
The One

Calcium (Ca2+) signaling plays a dichotomous role in cellular biology, controlling cell survival and proliferation on the one hand and cellular toxicity and cell death on the other. Store-operated Ca2+ entry (SOCE) by CRAC channels represents a major pathway for Ca2+ entry in non-excitable cells. The CRAC channel has two key components, the endoplasmic reticulum Ca2+ sensor stromal interaction molecule (STIM) and the plasma-membrane Ca2+ channel Orai. Physical coupling between STIM and Orai opens the CRAC channel and the resulting Ca2+ flux is regulated by a negative feedback mechanism of slow Ca2+ dependent inactivation (SCDI). The identification of the SOCE-associated regulatory factor (SARAF) and investigations of its role in SCDI have led to new functional and molecular insights into how SOCE is controlled. In this review, we provide an overview of the functional and molecular mechanisms underlying SCDI and discuss how the interaction between SARAF, STIM1, and Orai1 shapes Ca2+ signaling in cells.

scholarly journals Direct observation of a coil-to-helix contraction triggered by vinculin binding to talin

2020 ◽  
Vol 6 (21) ◽  
pp. eaaz4707 ◽  
Author(s):  
Rafael Tapia-Rojo ◽  
Alvaro Alonso-Caballero ◽  
Julio M. Fernandez
Keyword(s):  
Focal Adhesions ◽  
Interaction Force ◽  
Magnetic Tweezers ◽  
Feedback Mechanism ◽  
Force Transmission ◽  
Mechanical Coupling ◽  
Negative Feedback Mechanism ◽  
The Reformation ◽  
Energy Penalty ◽  
First Time

Vinculin binds unfolded talin domains in focal adhesions, which recruits actin filaments to reinforce the mechanical coupling of this organelle. However, it remains unknown how this interaction is regulated and its impact on the force transmission properties of this mechanotransduction pathway. Here, we use magnetic tweezers to measure the interaction between vinculin head and the talin R3 domain under physiological forces. For the first time, we resolve individual binding events as a short contraction of the unfolded talin polypeptide caused by the reformation of the vinculin-binding site helices, which dictates a biphasic mechanism that regulates this interaction. Force favors vinculin binding by unfolding talin and exposing the vinculin-binding sites; however, the coil-to-helix contraction introduces an energy penalty that increases with force, defining an optimal binding regime. This mechanism implies that the talin-vinculin-actin association could operate as a negative feedback mechanism to stabilize force on focal adhesions.

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