Liver glycogen-induced enhancements in hypoglycemic counterregulation require neuroglucopenia.

Author(s):  
Shana O Warner ◽  
Abby M Wadian ◽  
Marta S. Smith ◽  
Ben Farmer ◽  
Yufei Dai ◽  
...  

Iatrogenic hypoglycemia is a prominent barrier to achieving optimal glycemic control in patients with diabetes, in part due to dampened counterregulatory hormone responses. It has been demonstrated that elevated liver glycogen content can enhance these hormonal responses through signaling to the brain via afferent nerves, but the role that hypoglycemia in the brain plays in this liver glycogen effect remains unclear. During the first 4hrs of each study, the liver glycogen content of dogs was increased by using an intraportal infusion of fructose to stimulate hepatic glucose uptake (HG; n=13), or glycogen was maintained near fasting levels with a saline infusion (NG; n=6). After a 2hr control period, during which the fructose/saline infusion was discontinued, insulin was infused intravenously for an additional 2hrs to bring about systemic hypoglycemia in all animals, whereas brain euglycemia was maintained in a subset of the HG group by infusing glucose bilaterally into the carotid and vertebral arteries (HG-HeadEu; n=7). Liver glycogen content was markedly elevated in the two HG groups (43±4, 73±3 and 75±7 mg/g in NG, HG and HG-HeadEu, respectively). During the hypoglycemic period, arterial plasma glucose levels were indistinguishable between groups (53±2, 52±1 and 51±1 mg/dL, respectively), but jugular vein glucose levels were kept euglycemic (88±5 mg/dL) only in the HG-HeadEu group. Glucagon and epinephrine responses to hypoglycemia were higher in HG compared to NG, whereas despite the increase in liver glycogen, neither increased above basal in HG-HeadEu. These data demonstrate that the enhanced counterregulatory hormone secretion that accompanies increased liver glycogen content requires hypoglycemia in the brain.

1982 ◽  
Vol 243 (3) ◽  
pp. R450-R453
Author(s):  
W. Langhans ◽  
N. Geary ◽  
E. Scharrer

The effects of feeding on liver glycogen content and blood glucose in the hepatic and hepatic portal veins were investigated in rats. Liver glycogen content decreased about 25% during meals both in rats refed after 12 h food deprivation (23 +/- 1 to 17 +/- 1 mg glycogen/g liver) and in ad libitum-fed rats taking fully spontaneous meals (44 +/- 2 to 32 +/- 2 mg/g). Liver glycogen began to increase within 30 min after meals in ad libitum-fed rats. Hepatic vein blood glucose levels at meal onset (118 +/- 4 mg/dl in the food-deprived rats, 127 +/- 4 in ad libitum-fed rats) and at meal end (155 +/- 3 and 166 +/- 5 mg/dl, respectively) were similar in the two groups. Portal vein blood glucose increased during meals in the previously food-deprived rats (83 +/- 4 to 116 +/- 6 mg/dl) but not in the ad libitum-fed rats (127 +/- 5 to 132 +/- 3 mg/dl). Mechanisms that may elicit prandial glycogenolysis and the possible role of this effect in the production of meal ending satiety are discussed.


Planta Medica ◽  
2019 ◽  
Vol 85 (06) ◽  
pp. 465-472 ◽  
Author(s):  
Ivica Jeremic ◽  
Sasa Petricevic ◽  
Vanja Tadic ◽  
Dragana Petrovic ◽  
Jelena Tosic ◽  
...  

AbstractMenopause is characterized by deep metabolic disturbances, including decreased insulin sensitivity, adiposity, and changes in lipid profiles. Estrogen replacement therapy can partially reverse these changes, and while it is safe in most healthy postmenopausal women, there are still existing concerns regarding an increased risk for breast and endometrial cancer as well as a risk for cardiovascular and thromboembolic disease. Therefore, certain natural compounds with positive metabolic effects may be considered as a possible alternative or adjunctive treatment in patients not willing to take estrogens or patients with contraindications for estrogens. The aim of this study was to investigate the influence of Sideritis scardica (mountain tea) extract on metabolic disturbances induced by ovariectomy in rats. The study included 24 rats divided into three groups: ovariectomized rats treated with 200 mg/kg S. scardica extract for 24 weeks (n = 8), ovariectomized non-treated (n = 8), and Sham-operated (n = 8) rats. Food intake, weight gain, body composition, fasting glucose levels, response to oral glucose challenge, liver glycogen content, catalase activity, thiol groups, and malondialdehyde concentrations as well as AMP-activated protein kinase activity in liver cells were studied. Ovariectomized rats treated with S. scardica extract had lower blood triglycerides, reduced fasting glucose levels, as well lower glucose peaks after oral glucose challenge, increased liver glycogen content, and significantly higher catalase activity and thiol group concentration than non-treated ovariectomized rats. The ability of S. scardica extract to attenuate metabolic disturbances associated with ovariectomy was associated with the activation of AMP-activated protein kinase in liver cells.


1997 ◽  
Vol 273 (2) ◽  
pp. E262-E267 ◽  
Author(s):  
S. Metzger ◽  
N. Goldschmidt ◽  
V. Barash ◽  
T. Peretz ◽  
O. Drize ◽  
...  

Mice bearing interleukin-6 (IL-6)-secreting tumor were used to study the chronic effect of IL-6 on carbohydrate metabolism. Mice were injected with allogeneic tumor cells transduced with the murine IL-6 gene. Serum IL-6 levels were correlated exponentially with tumor weight. Secretion of IL-6 from the developed tumors was associated with decreased food consumption, reduced body weight, and reduced blood glucose levels. Insulin levels did not change, and 2-deoxyglucose uptake was not affected in most tissues examined. A significant increase of 2-deoxyglucose uptake was measured in the liver. Glycogen content in the liver determined 0, 6, 12, and 18 days after tumor inoculation was 42, 23, 12, and 3 mg/g, respectively. The activity of phosphoenolpyruvate carboxykinase was not affected. The activity of glucose-6-phosphatase (G-6-Phase) determined 6, 12, and 18 days after tumor injection was 84, 70, and 50% of G-6-Pase activity in pair-fed mice bearing nonsecreting tumors, respectively. G-6-Pase mRNA levels were markedly reduced due to inhibition of G-6-Pase gene transcriptional rate.


1981 ◽  
Vol 241 (5) ◽  
pp. R330-R335 ◽  
Author(s):  
N. Geary ◽  
W. Langhans ◽  
E. Scharrer

The suppression of food intake elicited in rats by injection of pancreatic glucagon and the accompanying changes in energy metabolite flux were investigated. Glucagon injections, 120-360 micrograms ip, were made as rats began the first meal of the dark phase after food deprivation during the light phase. Glucagon-injected rats terminated their meals sooner and ate smaller meals than vehicle-injected rats. For metabolic assays, rats were identically treated and killed just at meal onset or 15 min later. Portal vein blood glucose increased similarly in all rats allowed to feed, whereas plasma nonesterified fatty acid and D-(-)-3-hydroxybutyrate levels decreased during feeding. In contrast, hepatic vein and aorta blood glucose levels increased more after glucagon than after vehicle injections. Liver glycogen content decreased after glucagon injections. The highest glucagon dose only had slight lipolytic and ketogenic effects. It was concluded the glycogenolytic and hyperglycemic action of glucagon may generate a satiety signal sufficient to cause premature termination of meals. Changes in ketone and lipid fluxes do not appear necessary for this behavioral effect.


1989 ◽  
Vol 67 (11) ◽  
pp. 2746-2750 ◽  
Author(s):  
M. M. Vijayan ◽  
J. F. Leatherland

Coho salmon given intraperitoneal implants of hydrogenated coconut oil alone or coconut oil containing cortisol at 1, 5, or 10 mg/fish exhibited dose-related increases in plasma cortisol levels at day 15. After 30 days, plasma cortisol levels were significantly higher in the cortisol-implanted groups but there was no dose-related response. Plasma T3 levels were lowered in cortisol-treated fish, but plasma T4 levels were not consistently affected. Plasma glucose levels were significantly higher in the group treated with cortisol at 10 mg/fish than in the controls on both sampling days, whereas liver glycogen content and hepatosomatic index were significantly lower in the cortisol-treated groups at day 30 but not at day 15. Plasma protein levels were not significantly different between treatments at either sampling time. The splenosomatic indices were not significantly different in the three treatment groups at day 15, but at day 30 the values in the 5 and 10 mg/fish cortisol-treated groups were significantly higher than in the controls.


Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1801-P
Author(s):  
KRISTINA WARDELMANN ◽  
JOSÉ PEDRO CASTRO ◽  
MICHAELA RATH ◽  
JÜRGEN WEIß ◽  
ANNETTE SCHUERMANN ◽  
...  

1960 ◽  
Vol 38 (1) ◽  
pp. 553-558 ◽  
Author(s):  
Violet M. Chang ◽  
D. R. Idler

Liver glycogen levels were determined for a pure stock of sockeye salmon (Oncorhynchus nerka) taken at three locations during spawning migration. The liver glycogen content of the male was found to be consistently greater than that of the female throughout the entire river migration. In both sexes liver glycogen decreased during the earlier phase of migration, but increased during the later stage so that the levels at the spawning grounds were approximately twice those at the mouth of the river. The changes which occur are discussed in relation to sex differences, energy expenditures, and plasma steroid hormone levels.


Development ◽  
1971 ◽  
Vol 25 (3) ◽  
pp. 377-384
Author(s):  
Nicole Daugéras

Influence of thiourea on the glycogen content of the liver of the chick embryo In the developing chick embryo, liver glycogen appears on the sixth day of incubation. The glycogen content increases from the sixth day, but decreases on the twelfth day before increasing again. This decrease on day 12 might be related to the onset of thyroid activity, which would be responsible for an increased rate of utilization of the substrates. An antithyroid drug, thiourea, has been injected on day 6·0. The liver glycogen concentration of the thiourea-treated chick embryos was determined from the tenth to the fifteenth days and compared with that of the control embryos. (i) On days 11 and 12 the liver glycogen concentration of the injected embryos is higher than that of the controls. (ii) On day 13 the liver glycogen level of treated embryos decreases; this decrease might be correlated with possible functional activity of the thyroid glands if their biosynthesis is no longer inhibited by the thiourea injection or with thyroid hormones possibly coming from the yolk. (iii) On days 14 and 15 no difference is observed between the liver glycogen content of the thiourea-treated embryos and that of the controls.


Author(s):  
Pratik Choudhary ◽  
Stephanie A. Amiel

Hypoglycaemia (low blood glucose concentration) is the most important acute complication of the pharmacological treatment of diabetes mellitus. Low blood glucose impairs brain (and, potentially, cardiac) function. The brain has minimal endogenous stores of energy, with small amounts of glycogen in astroglial cells. The brain is therefore largely dependent on circulating glucose as the substrate to fuel cerebral metabolism and support cognitive performance. If blood glucose levels fall sufficiently, cognitive dysfunction is inevitable. In health, efficient glucose sensing and counterregulatory mechanisms exist to prevent clinically significant hypoglycaemia. These are impaired by diabetes and by its therapies. Patients with diabetes rank fear of hypoglycaemia as highly as fear of chronic complications such as nephropathy or retinopathy (1). Fear of hypoglycaemia, hypoglycaemia itself and attempts to avoid hypoglycaemia limit the degree to which glycaemic control can be intensified to reduce the risk of chronic complications of diabetes both for type 1 and type 2 diabetes.


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