EFFECTS OF INSULIN, GLUCAGON, AND INSULIN/GLUCAGON INFUSIONS ON LIVER MORPHOLOGY AND CELL DIVISION AFTER COMPLETE PORTACAVAL SHUNT IN DOGS

Insulin, glucagon, and insulin/glucagon mixtures have been infused for four days into the left portal vein of dogs after portacaval shunt. In the left but not the right liver lobes, insulin alone reduced atrophy, preserved hepatocyte ultrastructure, and trebled cell renewal. Glucagon alone had no effect. In small doses, glucagon did not potentiate the action of insulin and in large doses it may have reduced the insulin benefit. These studies explain the development of the previously mysterious Eck fistula syndrome, provide clues about in-vivo cell growth control by hormones, and suggest new lines of inquiry about the pathogenesis and/or treatment of several human disease processes. © 1976

Cyclic AMP metabolism and adenylate cyclase concentration in patients with advanced hepatic cirrhosis

Glucagon was tested for its effect on plasma adenosine 3′,5′-cyclic monophosphate (cyclic AMP), insulin, and glucose in healthy subjects and in patients with advanced cirrhosis of the liver. In the normal subjects, intravenous infusion of glucagon caused a significant increase in plasma cyclic AMP, glucose, and insulin. In advanced cirrhotics, plasma cyclic AMP, glucose, and insulin did not increase. Adenylate cyclase concentration was measured in liver tissue from end stage cirrhotic patients and from brain-dead organ donors whose cardiovascular function was maintained in a stable state. Basal and total adenylate cyclase concentration were not different in the two groups. Adenylate cyclase from the livers of advanced cirrhotics was, however, significantly less responsive to glucagon stimulation than was that from donor livers. Hepatocytes in advanced cirrhosis have abnormal metabolic behavior characterized by abnormal adenylate cyclase-cyclic AMP response to hormonal stimulation. © 1978

The effect of pre-exercise galactose and glucose ingestion on high-intensity endurance cycling.

This study evaluated the effects of the pre-exercise (30 minutes) ingestion of galactose (Gal) or glucose (Glu) on endurance capacity as well as glycemic and insulinemic responses. Ten trained male cyclists completed 3 randomized high-intensity cycling endurance tests. Thirty minutes before each trial, cyclists ingested 1 L of either 40 g of glucose, 40 g of galactose, or a placebo in a double-blind manner. The protocol comprised 20 minutes of progressive incremental exercise (70-85% maximal power output [Wmax]); ten 90-second bouts at 90% Wmax, separated by 180 seconds at 55% Wmax; and 90% Wmax until exhaustion. Blood samples were drawn throughout the protocol. Times to exhaustion were longer with Gal (68.7 ± 10.2 minutes, p = 0.005) compared with Glu (58.5 ± 24.9 minutes), with neither being different to placebo (63.9 ± 16.2 minutes). Twenty-eight minutes after Glu consumption, plasma glucose and serum insulin concentrations were higher than with Gal and placebo (p < 0.001). After the initial 20 minutes of exercise, plasma glucose concentrations increased to a relative hyperglycemia during the Gal and placebo, compared with Glu condition. Higher plasma glucose concentrations during exercise, and the attenuated serum insulin response at rest, may explain the significantly longer times to exhaustion produced by Gal compared with Glu. However, neither carbohydrate treatment produced significantly longer times to exhaustion than placebo, suggesting that the pre-exercise ingestion of galactose and glucose alone is not sufficient to support this type of endurance performance

Carbon-13 Dynamic MRS and MRSI of Normal and Fasted Rat Liver with Hyperpolarized C-Pyruvate

BACKGROUND: The use of in vivo (13)C nuclear magnetic resonance spectroscopy in probing metabolic pathways to study normal metabolism and characterize disease physiology has been limited by its low sensitivity. However, recent technological advances have enabled greater than 50,000-fold enhancement of liquid-state polarization of metabolically active (13)C substrates, allowing for rapid assessment of (13)C metabolism in vivo. The present study applied hyperpolarized (13)C magnetic resonance spectroscopy to the investigation of liver metabolism, demonstrating for the first time the feasibility of applying this technology to detect differences in liver metabolic states. PROCEDURES: [1-(13)C]pyruvate was hyperpolarized with a dynamic nuclear polarization instrument and injected into normal and fasted rats. The uptake of pyruvate and its conversion to the metabolic products lactate and alanine were observed with slice-localized dynamic magnetic resonance spectroscopy and 3D magnetic resonance spectroscopic imaging (3D-MRSI). RESULTS: Significant differences in lactate to alanine ratio (P < 0.01) between normal and fasted rat liver slice dynamic spectra were observed. 3D-MRSI localized to the fasted livers demonstrated significantly decreased (13)C-alanine levels (P < 0.01) compared to normal. CONCLUSIONS: This study presents the initial demonstration of characterizing metabolic state differences in the liver with hyperpolarized (13)C spectroscopy and shows the ability to detect physiological perturbations in alanine aminotransferase activity, which is an encouraging result for future liver disease investigations with hyperpolarized magnetic resonance technology

The effect of pre-exercise galactose and glucose ingestion on high-intensity endurance cycling.

This study evaluated the effects of the pre-exercise (30 minutes) ingestion of galactose (Gal) or glucose (Glu) on endurance capacity as well as glycemic and insulinemic responses. Ten trained male cyclists completed 3 randomized high-intensity cycling endurance tests. Thirty minutes before each trial, cyclists ingested 1 L of either 40 g of glucose, 40 g of galactose, or a placebo in a double-blind manner. The protocol comprised 20 minutes of progressive incremental exercise (70-85% maximal power output [Wmax]); ten 90-second bouts at 90% Wmax, separated by 180 seconds at 55% Wmax; and 90% Wmax until exhaustion. Blood samples were drawn throughout the protocol. Times to exhaustion were longer with Gal (68.7 ± 10.2 minutes, p = 0.005) compared with Glu (58.5 ± 24.9 minutes), with neither being different to placebo (63.9 ± 16.2 minutes). Twenty-eight minutes after Glu consumption, plasma glucose and serum insulin concentrations were higher than with Gal and placebo (p < 0.001). After the initial 20 minutes of exercise, plasma glucose concentrations increased to a relative hyperglycemia during the Gal and placebo, compared with Glu condition. Higher plasma glucose concentrations during exercise, and the attenuated serum insulin response at rest, may explain the significantly longer times to exhaustion produced by Gal compared with Glu. However, neither carbohydrate treatment produced significantly longer times to exhaustion than placebo, suggesting that the pre-exercise ingestion of galactose and glucose alone is not sufficient to support this type of endurance performance

Substrate cycling between de novo lipogenesis and lipid oxidation: a thermogenic mechanism against skeletal muscle lipotoxicity and glucolipotoxicity

Life is a combustion, but how the major fuel substrates that sustain human life compete and interact with each other for combustion has been at the epicenter of research into the pathogenesis of insulin resistance ever since Randle proposed a 'glucose-fatty acid cycle' in 1963. Since then, several features of a mutual interaction that is characterized by both reciprocality and dependency between glucose and lipid metabolism have been unravelled, namely: 1. the inhibitory effects of elevated concentrations of fatty acids on glucose oxidation (via inactivation of mitochondrial pyruvate dehydrogenase or via desensitization of insulin-mediated glucose transport), 2. the inhibitory effects of elevated concentrations of glucose on fatty acid oxidation (via malonyl-CoA regulation of fatty acid entry into the mitochondria), and more recently 3. the stimulatory effects of elevated concentrations of glucose on de novo lipogenesis, that is, synthesis of lipids from glucose (via SREBP1c regulation of glycolytic and lipogenic enzymes). This paper first revisits the physiological significance of these mutual interactions between glucose and lipids in skeletal muscle pertaining to both blood glucose and intramyocellular lipid homeostasis. It then concentrates upon emerging evidence, from calorimetric studies investigating the direct effect of leptin on thermogenesis in intact skeletal muscle, of yet another feature of the mutual interaction between glucose and lipid oxidation: that of substrate cycling between de novo lipogenesis and lipid oxidation. It is proposed that this energy-dissipating substrate cycling that links glucose and lipid metabolism to thermogenesis could function as a 'fine-tuning' mechanism that regulates intramyocellular lipid homeostasis, and hence contributes to the protection of skeletal muscle against lipotoxicity

STC1 and PTHrP modify carbohydrate and lipid metabolism in liver of a teleost fish

Stanniocalcin 1 (STC1) and parathyroid hormone-related protein (PTHrP) are calciotropic hormones in vertebrates. Here, a recently hypothesized metabolic role for these hormones is tested on European sea bass treated with: (i) teleost PTHrP(1-34), (ii) PTHrP(1-34) and anti-STC1 serum (pro-PTHrP groups), (iii) a PTHrP antagonist PTHrP(7-34) or (iv) PTHrP(7-34) and STC1 (pro-STC1 groups). Livers were analysed using untargeted metabolic profiling based on proton nuclear magnetic resonance (1H-NMR) spectroscopy. Concentrations of branched-chain amino acid (BCAA), alanine, glutamine and glutamate increased in pro-STC1 groups suggesting their mobilization from the muscle to the liver for degradation and gluconeogenesis from alanine and glutamine. In addition, only STC1 treatment decreased the concentrations of succinate, fumarate and acetate, indicating slowing of the citric acid cycle. In the pro-PTHrP groups the concentrations of glucose, erythritol and lactate decreased, indicative of gluconeogenesis from lactate. Taurine, trimethylamine, trimethylamine N-oxide and carnitine changed in opposite directions in the pro-STC1 versus the pro-PTHrP groups, suggesting opposite effects, with STC1 stimulating lipogenesis and PTHrP activating lipolysis/β-oxidation of fatty acids. These findings suggest a role for STC1 and PTHrP related to strategic energy mechanisms that involve the production of glucose and safeguard of liver glycogen reserves for stressful situations.Portuguese Foundation for Science and Technology (FCT) SFRH/BD/103185/2014info:eu-repo/semantics/publishedVersio