Chronic and transitional regulation of gluconeogenesis and glyconeogenesis by insulin and glucagon in neonatal calf hepatocytes.

Abstract

Milk-fed calves were used as a source of hepatocytes to establish monlayers to test the effects of chronic (41 h) incubation with no hormone, 100 nM insulin, or 100 nM glucagon on gluconeogenesis (glucose retained as glycogen plus glucose released into the medium) from 2.5 mM [2-(14)C]propionate and 2.0 mM [U-14C]lactate (1.0 mM lactate plus 1.0 mM pyruvate) during a subsequent 3-h (acute) incubation. Media for acute incubations contained no hormone, 0 or 10 nM insulin, or 0, 1, 10, or 100 mM glucagon. Chronic glucagon increased gluconeogenesis from propionate and glyconeogenesis from propionate and lactate compared with chronic exposure to medium with no hormone. A chronic glucagon x acute hormone interaction was manifested as an augmented response to acute glucagon on gluconeogenesis from propionate; a similar potentiation was not evident for gluconeogenesis from lactate. The concentration of glucagon required to acutely stimulate gluconeogenesis was increased by prior incubation with glucagon. Acute glucagon decreased the flux of glucose retained as glycogen regardless of chronic hormone treatment. Chronic incubation with insulin diminished the stimulatory effects of glucagon on gluconeogenesis from lactate. Chronic incubation with insulin did not alter the sensitivity or responsiveness at acute glucagon of gluconeogenesis from propionate. The data demonstrate persisting changes that favor increased basal gluconeogenesis from propionate with chronically elevated glucagon coupled to an increased capacity to respond acutely to glucagon and opposing chronic actions of insulin on lactate metabolism. These data suggest that insulin and glucagon target separate pathways that are unique to metabolism of propionate and lactate.

Maturation of endogenous glucose production in preterm and term calves

“…Therefore, gluconeogenic enzymes were differently affected by metabolic and endocrine changes and supported the findings in dairy cows (Hammon et al, 2009) that changes of gluconeogenic enzymes may be differently regulated. Furthermore, the abovementioned impairment of endocrine regulation on eGP in neonatal calves is probably reflected by the low endocrine response on gluconeogenic enzymes (Donkin et al, 1997;Scheuer et al, 2006). Changes in PEPCK activities indicate that this enzyme likely was a rate-limiting enzyme, but other gluconeogenic enzyme activities measured herein were more or less unaffected by changes in ontogenic state.…”

“…Plasma lactate is decreased more after delivery by section in term-born calves than in preterm calves (Sangild et al, 2000), which confirms our observations. Elevated plasma lactate concentrations may indicate less oxygen consumption or less lactate utilization; for example, as substrate for GNG or energy fuel, in PT calves, because lactate is an important substrate for GNG in neonates (Donkin et al, 1997). In addition, lactate serves as a substrate for the TCA cycle (Voet and Voet, 1994).…”

Endocrine And Metabolic Adaptations Of Calves To Extra-Uterine Life

“…As previously mentioned glycogen mobilization is provoked mainly by catecholamine increase supported by a decreased insulin/ glucagon molar ratio. There is a lot of evidence that proves that glucagon by itself is ineffective in triggering neonatal liver glycogenolisys [44,45]. The partial resistance to glucagon stimulation by neonatal (and also fetal) hepatocytes could be due to (a) the lower number of high affi nity receptors, or (b) an impaired coupling of the receptor with adenilate cyclase [46].…”

Insulin and Glucagon Secretory Patterns during Propionate and Arginine Tolerance Tests in Japanese Black Cattle with Growth Retardation

“…Circulating insulin and glucagon concentrations are linked to synthesis of glucose, which is a major source of energy in ruminants, and the energy status can be estimated from the insulin/glucagon concentration ratio [8]. The insulin/glucagon concentration ratio is responsive to physiological condition such as growth, lactation, diet, and feeding patterns [3]. The cattle with growth retardation in this study showed lower insulin and normal glucagon concentrations immediately before injections, resulting in lower insulin/ glucagon concentration ratios than in the control.…”