Comparison of insulins detemir and glargine: effects on glucose disposal, hepatic glucose release and the central nervous system.

AIMS: The effects of insulins detemir (Det) and glargine (Glar) on endogenous glucose production (EGP) and net hepatic glucose output (NHGO) were compared. METHODS: Arteriovenous difference and tracer ([3-(3) H]glucose) techniques were employed during a two-step hyperinsulinemic euglycaemic clamp in conscious dogs (6 groups, n = 5-6/group). After equilibration and basal sampling (0-120 min), somatostatin was infused and basal glucagon was replaced intraportally. Det or Glar was infused via portal vein (Po), peripheral vein (IV), or bilateral carotid and vertebral arteries (H) at 0.1 and 0.3 mU/kg/min (low Insulin; Glar vs. Det, respectively, 120-420 min) and 4× the low insulin rate (high insulin; 420-540 min). RESULTS: NHGO and EGP were suppressed and glucose R(d) and infusion rate were stimulated similarly by Det and Glar at both Low and high insulin with each infusion route. Non-esterified fatty acid (NEFA) concentrations during low insulin were 202 ± 37 versus 323 ± 75 µM in DetPo and GlarPo (p < 0.05) and 125 ± 39 versus 263 ± 48 µM in DetIV and GlarIV, respectively (p < 0.05). In DetH versus GlarH, pAkt/Akt (1.7 ± 0.2 vs. 1.0 ± 0.2) and pSTAT3/STAT3 (1.4 ± 0.2 vs. 1.0 ± 0.1) were significantly increased in the liver but not in the hypothalamus. CONCLUSIONS: Det and Glar have similar net effects on acute regulation of hepatic glucose metabolism in vivo regardless of delivery route. Portal and IV detemir delivery reduces circulating NEFA to a greater extent than glargine, and head detemir infusion enhances molecular signalling in the liver. These findings indicate a need for further examination of Det's central and hepatic effects.

Evolution of mechanisms controlling mating behavior.

The proximate mechanisms underlying mating behavior in naturally occurring species can be fundamentally different from those in more commonly studied laboratory and domesticated forms. In naturally occurring species, reproductive strategies are much more diverse, and mechanisms controlling behavior are correspondingly diverse. A variety of hormonal, environmental, and social cues can be used to activate mating behavior. Which cues are used by particular species depends on differences in environmental and physiological constraints imposed by particular reproductive strategies. Study of this diversity of mechanisms promises to identify specific selective forces that have shaped their evolution. This evolutionary perspective leads to widely applicable generalizations and provides a useful context within which to conceptualize differences between species, populations, and individuals.

Sex Differences in Cognitive Flexibility and Resting Brain Networks in Middle-Aged Marmosets.

Sex differences in human cognitive performance are well characterized. However, the neural correlates of these differences remain elusive. This issue may be clarified using nonhuman primates, for which sociocultural influences are minimized. We used the marmoset (Callithrix jacchus) to investigate sex differences in two aspects of executive function: reversal learning and intradimensional/extradimensional (ID/ED) set shifting. Stress reactivity and motor function were also assessed. In agreement with human literature, females needed more trials than males to acquire the reversals. No sex differences in ED set shifting or motivational measures were observed. The findings suggest enhanced habit formation in females, perhaps due to striatal estrogenic effects. Both sexes showed increased urinary cortisol during social separation stressor, but females showed an earlier increase in cortisol and a greater increase in agitated locomotion, possibly indicating enhanced stress reactivity. Independent of sex, basal cortisol predicted cognitive performance. No sex differences were found in motor performance. Associations between brain networks and reversal learning performance were investigated using resting state fMRI. Resting state functional connectivity (rsFC) analyses revealed sex differences in cognitive networks, with differences in overall neural network metrics and specific regions, including the prefrontal cortex, caudate, putamen, and nucleus accumbens. Correlations between cognitive flexibility and neural connectivity indicate that sex differences in cognitive flexibility are related to sex-dependent patterns of resting brain networks. Overall, our findings reveal sex differences in reversal learning, brain networks, and their relationship in the marmoset, positioning this species as an excellent model to investigate the biological basis of cognitive sex differences.

Comparison of the time courses of insulin and the portal signal on hepatic glucose and glycogen metabolism in the conscious dog.

To investigate the temporal response of the liver to insulin and portal glucose delivery, somatostatin was infused into four groups of 42-h-fasted, conscious dogs (n = 6/group), basal insulin and glucagon were replaced intraportally, and hyperglycemia was created via a peripheral glucose infusion for 90 min (period 1). This was followed by a 240-min experimental period (period 2) in which hyperglycemia was matched to period 1 and either no changes were made (CON), a fourfold rise in insulin was created (INS), a portion of the glucose (22.4 mumol.kg-1.min-1) was infused via the portal vein (Po), or a fourfold rise in insulin was created in combination with portal glucose infusion (INSPo). Arterial insulin levels were similar in all groups during period 1 (approximately 45 pM) and were 45 +/- 9, 154 +/- 20, 43 +/- 7, and 128 +/- 14 pM during period 2 in CON, INS, Po, and INSPo, respectively. The hepatic glucose load was similar between periods and among groups (approximately 278 mumol.kg-1.min-1). Net hepatic glucose output was similar among groups during period 1 (approximately 0.1 mumol.kg-1.min-1) and did not change significantly in CON during period 2. In INS net hepatic glucose uptake (NHGU; mumol.kg-1.min-1) was -3.8 +/- 3.3 at 15 min of period 2 and did not reach a maximum (-15.9 +/- 6.6) until 90 min. In contrast, NHGU reached a maximum of -13.0 +/- 3.7 in Po after only 15 min of period 2. In INSPo, NHGU reached a maximum (-23.6 +/- 3.5) at 60 min. Liver glycogen accumulation during period 2 was 21 +/- 10, 84 +/- 17, 65 +/- 16, and 134 +/- 17 mumol/gram in CON, INS, Po, and INSPo, respectively. The increment (period 1 to period 2) in the active form of liver glycogen synthase was 0.7 +/- 0.4, 6.5 +/- 1.2, 2.8 +/- 1.0, and 8.5 +/- 1.3% in CON, INS, Po, and INSPo, respectively. Thus, in contrast to insulin, the portal signal rapidly activates NHGU. In addition, the portal signal independent of a rise in insulin, can cause glycogen accumulation in the liver.

Sources of carbon for hepatic glycogen synthesis in the conscious dog.

To identify the source(s) of carbon for the indirect pathway of hepatic glycogen synthesis, we studied nine 42-h fasted conscious dogs given a continuous intraduodenal infusion of glucose, labeled with [1-13C]glucose and [3-3H]glucose, at 8 mg.kg-1.min-1 for 240 min. Glycogen formation by the direct pathway was measured by 13C-NMR. Net hepatic balances of glucose, gluconeogenic amino acids, lactate, and glycerol were determined using the arteriovenous difference technique. During the steady-state period (the final hour of the infusion), 81% of the glucose infused was absorbed as glucose. Net gut output of lactate and alanine accounted for 5% and 3% of the glucose infused, respectively. The cumulative net hepatic uptakes were: glucose, 15.5 +/- 3.8 g; gluconeogenic amino acids, 32.2 +/- 2.2 mmol (2.9 +/- 0.2 g of glucose equivalents); and glycerol, 6.1 +/- 0.9 mmol (0.6 +/- 0.1 g of glucose equivalents). The liver produced a net of 29.2 +/- 9.6 mmol of lactate (2.6 +/- 0.8 g of glucose equivalents). Net hepatic glycogen synthesis totaled 9.3 +/- 2.5 g (1.8 +/- 0.4 g/100 g liver), with the direct pathway being responsible for 57 +/- 10%. Thus, net hepatic glucose uptake was sufficient to account for all glycogen formed by both the direct and indirect pathways. Total net hepatic uptake of gluconeogenic precursors (gluconeogenic amino acids, glycerol, and lactate) was able to account for only 20% of net glycogen synthesis by the indirect pathway. In a net sense, our data are consistent with an intrahepatic origin for most of the three-carbon precursors used for indirect glycogen synthesis.

Regulation of hepatic metabolism by enteral delivery of nutrients.

The liver plays a unique role in nutrient homeostasis. Its anatomical location makes it ideally suited to control the systemic supply of absorbed nutrients, and it is the primary organ that can both consume and produce substantial amounts of glucose. Moreover, it is the site of a substantial fraction (about 25 %) of the body's protein synthesis, and the liver and other organs of the splanchnic bed play an important role in sparing dietary N by storing ingested amino acids. This hepatic anabolism is under the control of hormonal and nutritional changes that occur during food intake. In particular, the route of nutrient delivery, i.e. oral (or intraportal) v. peripheral venous, appears to impact upon the disposition of the macronutrients and also to affect both hepatic and whole-body nutrient metabolism. Intraportal glucose delivery significantly enhances net hepatic glucose uptake, compared with glucose infusion via a peripheral vein. On the other hand, concomitant intraportal infusion of both glucose and gluconeogenic amino acids significantly decreases net hepatic glucose uptake, compared with infusion of the same mass of glucose by itself. Delivery of amino acids via the portal vein may enhance their hepatic uptake, however. Elevation of circulating lipids under postprandial conditions appears to impair both hepatic and whole-body glucose disposal. Thus, the liver's role in nutrient disposal and metabolism is highly responsive to the route of nutrient delivery, and this is an important consideration in planning nutrition support and optimising anabolism in vulnerable patients.

Insulin is required for the liver to respond to intraportal glucose delivery in the conscious dog.

To determine whether insulin is essential for the augmented hepatic glucose uptake observed in the presence of intraportal glucose delivery, SRIF was used to induce acute insulin deficiency in 5 conscious dogs, and glucose was infused into the portal vein or a peripheral vein in two sequential, randomized periods. Insulin and C-peptide levels were below the limits of detection after SRIF infusion, and the load of glucose presented to the liver was approximately doubled and equivalent during the portal and peripheral periods. Net hepatic glucose output was 2.9 +/- 0.9 and 2.1 +/- 1.1 mumol.kg-1.min-1 during portal and peripheral glucose delivery, respectively. In an additional set of protocols, pancreatectomized dogs were used to investigate the effects of prolonged insulin deficiency (n = 5) and acute insulin replacement (n = 4) on the hepatic response to intraportal glucose delivery. In the prolonged insulin deficiency protocol, SRIF was used to lower glucagon and thereby reduce circulating glucose levels, and glucose was infused into the portal or peripheral circulations in two sequential, randomized periods. As with acute insulin deficiency, net hepatic glucose output was still evident and similar (3.6 +/- 1.1 and 4.2 +/- 1.3 mumol.kg-1.min-1) during portal and peripheral glucose delivery, respectively. When the pancreatectomized dogs were restudied using a similar protocol, but one in which insulin was replaced (4X-basal), and the glucose load to the liver was matched to that which occurred in the prolonged insulin deficiency protocol, net hepatic glucose uptake was 23.6 +/- 6.1 mumol.kg-1.min-1 during portal glucose delivery but only 10.3 +/- 3.5 mumol.kg-1.min-1 during peripheral glucose delivery. These results suggest that the induction of net hepatic glucose uptake and the augmented hepatic response to intraportal glucose delivery require the presence of insulin.

Magnitude of negative arterial-portal glucose gradient alters net hepatic glucose balance in conscious dogs.

To examine the relationship between the magnitude of the negative arterial-portal glucose gradient and net hepatic glucose uptake, two groups of 42-h fasted, conscious dogs were infused with somatostatin, to suppress endogenous insulin and glucagon secretion, and the hormones were replaced intraportally to create hyperinsulinemia (3- to 4-fold basal) and basal glucagon levels. The hepatic glucose load to the liver was doubled and different negative arterial-portal glucose gradients were established by altering the ratio between portal and peripheral vein glucose infusions. In protocol 1 (n = 6) net hepatic glucose uptake was 42.2 +/- 6.7, 35.0 +/- 3.9, and 33.3 +/- 4.4 mumol.kg-1.min-1 at arterial-portal plasma glucose gradients of -4.1 +/- 0.9, -1.8 +/- 0.4, and -0.8 +/- 0.1 mM, respectively. In protocol 2 (n = 6) net hepatic glucose uptake was 26.1 +/- 2.8 and 12.2 +/- 1.7 mumol.kg-1.min-1 at arterial-portal plasma glucose gradients of -0.9 +/- 0.2 and -0.4 +/- 0.1 mM, respectively. No changes in the hepatic insulin or glucose loads were evident within a given protocol. Although net hepatic glucose uptake was lower in protocol 2 when compared with protocol 1 (26.1 +/- 2.8 vs. 33.3 +/- 4.4 mumol.kg-1.min-1) in the presence of a similar arterial-portal plasma glucose gradient (-0.9 vs. -0.8 mM) the difference could be attributed to the hepatic glucose load being lower in protocol 2 (i.e., hepatic fractional glucose extraction was not significantly different) primarily as a result of lower hepatic blood flow. In conclusion, in the presence of fixed hepatic glucose and insulin loads, the magnitude of the negative arterial-portal glucose gradient can modify net hepatic glucose uptake in vivo.

Acute fructose administration improves oral glucose tolerance in adults with type 2 diabetes.

OBJECTIVE: In normal adults, a small (catalytic) dose of fructose administered with glucose decreases the glycemic response to a glucose load, especially in those with the poorest glucose tolerance. We hypothesized that an acute catalytic dose of fructose would also improve glucose tolerance in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: Five adults with type 2 diabetes underwent an oral glucose tolerance test (OGTT) on two separate occasions, at least 1 week apart. Each OGTT consisted of 75 g glucose with or without the addition of 7.5 g fructose (OGTT + F or OGTT - F), in random order. Arterialized blood samples were collected from a heated dorsal hand vein twice before ingestion of the carbohydrate and every 15 min for 3 h afterward. RESULTS: The area under the curve (AUC) of the plasma glucose response was reduced by fructose administration in all subjects; the mean AUC during the OGTT + F was 14% less than that during the OGTT - F (P < 0.05). The insulin AUC was decreased 21% with fructose administration (P = 0.2). Plasma glucagon concentrations declined similarly during OGTT - F and OGTT + F. The incremental AUC of the blood lactate response during the OGTT - F was approximately 50% of that observed during the OGTT + F (P < 0.05). Neither nonesterified fatty acid nor triglyceride concentrations differed between the two OGTTs. CONCLUSIONS: Low-dose fructose improves the glycemic response to an oral glucose load in adults with type 2 diabetes, and this effect is not a result of stimulation of insulin secretion.

Acute fructose administration decreases the glycemic response to an oral glucose tolerance test in normal adults.

In animal models, a small (catalytic) dose of fructose administered with glucose decreases the glycemic response to the glucose load. Therefore, we examined the effect of fructose on glucose tolerance in 11 healthy human volunteers (5 men and 6 women). Each subject underwent an oral glucose tolerance test (OGTT) on 2 separate occasions, at least 1 week apart. Each OGTT consisted of 75 g glucose with or without 7.5 g fructose (OGTT+F or OGTT-F), in random order. Arterialized blood samples were obtained from a heated dorsal hand vein twice before ingestion of the carbohydrate and every 15 min for 2 h afterward. The area under the curve (AUC) of the change in plasma glucose was 19% less in OGTT+F vs. OGTT-F (P: < 0.05). Glucose tolerance was improved by fructose in 9 subjects and worsened in 2. All 6 subjects with the largest glucose AUC during OGTT-F had a decreased response during OGTT+F (31 +/- 5% decrease). The insulin AUC did not differ between the 2 studies. Of the 9 subjects with improved glucose tolerance during the OGTT+F, 5 had smaller insulin AUC during the OGTT+F than the OGTT-F. Plasma glucagon concentrations declined similarly during OGTT-F and OGTT+F. The blood lactate response was about 50% greater during the OGTT+F (P: < 0.05). Neither nonesterified fatty acid nor triglyceride concentrations differed between the two OGTT. In conclusion, low dose fructose improves the glycemic response to an oral glucose load in normal adults without significantly enhancing the insulin or triglyceride response. Fructose appears most effective in those normal individuals who have the poorest glucose tolerance.

Sodium induces hypertrophy of cultured myocardial myoblasts and vascular smooth muscle cells.

The mechanisms of sodium-induced myocardial hypertrophy and vascular hypertrophy are poorly understood. We tested the hypothesis that a high sodium concentration can directly induce cellular hypertrophy. Neonatal rat myocardial myoblasts (MMbs) and vascular smooth muscle cells (VSMCs) were cultured in a 50:50 mixture of DMEM and M199 supplemented with 10% fetal bovine serum. When the monolayers reached approximately 80% confluence, normal sodium medium (146 mmol/L) was replaced with high sodium media (152 mmol/L, 160 mmol/L, and 182 mmol/L) for up to 5 days. Increasing sodium from a baseline concentration of 146 mmol/L to the higher concentrations for 5 days caused dose-related increases in cell mean diameter, cell volume, and cellular protein content in both MMbs and VSMCs. Increasing the sodium concentration by only 4% (from 146 mmol/L to 152 mmol/L) caused the following respective changes in MMbs and VSMCs: 8.5% and 8.7% increase in cell mean diameter, 27.6% and 27.0% increase in cell volume, and 55.7% and 46.7% increase in cellular protein content. The rate of protein synthesis, expressed as [3H]leucine incorporation, increased by 87% and 99% in MMbs after exposure to 152 mmol/L and 160 mmol/L sodium, respectively, compared with the 146-mmol/L sodium control group. Exposure of MMbs to medium with a sodium concentration of 10% above normal, ie, 160 mmol/L, caused a significant decrease (range, 26% to 44%) in the rate of protein degradation at multiple time points over a 48-hour period compared with normal sodium control cells. The increase in cellular protein content caused by 160 mmol/L sodium returned to normal within 3 days after MMbs were returned to a normal sodium medium. These findings support the hypothesis that sodium has a direct effect to induce cellular hypertrophy and may therefore be an important determinant in causing myocardial and/or vascular hypertrophy in subjects with increased sodium concentration in the extracellular fluid.

Enteral-tube feeding as adjunct therapy in malnourished patients with cystic fibrosis: a clinical study and literature review.

Eight children (aged 8 mo to 13 yr) with cystic fibrosis (CF) and growth failure were given home nocturnal nasogastric feeding of an elemental diet for 3 mo and re-evaluated 3 mo after cessation of tube feeding. An increase in energy intake (p less than 0.05) resulted in increased serum transferrin (p less than 0.005), retinol-binding protein (p less than 0.05), and clinical scores (p less than 0.05) during the study. Height and growth velocity increased by 60% (p less than 0.05), and weight growth velocity increased by 63%. Arm-muscle circumference, triceps skinfolds, serum albumin, vitamin A, vitamin E, zinc, and copper did not change significantly during tube feeding. Nocturnal feeding were safe and effective in promoting growth; however, most children with severe lung disease did not sustain the gains after cessation of tube feeding. Our findings indicate that continued nutritional support is needed to maintain the growth in malnourished children with severe lung disease.

Temporal patterns of limbic monoamine and plasma corticosterone response during social stress.

Dominant and subordinate males respond differently to the stress of social interaction. After an hour of social interaction, subordinate male Anolis carolinensis have elevated serotonergic activity in hippocampus, but dominant males do not. In other species, and using other stressors, the activation of hippocampal serotonergic activity is much more rapid than one hour. To elucidate early stress responsiveness, adult male A. carolinensis were divided into four groups: isolated controls, and pairs of males sampled after 10, 20 or 40 minutes of aggressive interaction. Development of dominant-subordinate relationships was determined by behavior and by the celerity of eyespot darkening. Serotonergic activity in the hippocampus, nucleus accumbens and amygdala was elevated rapidly and equally in both dominant and subordinate males, as were plasma corticosterone concentrations. Serotonergic activity remained elevated through 40 minutes in hippocampus and nucleus accumbens. Only subordinate males had elevated corticosterone levels at 40 minutes. Social status does not impede socially induced stress responses. Rather, rapid regulation of serotonergic stress responses appears to be a mediating factor in determining both behavioral output and social status. Temporal expressions of monoaminergic and endocrine stress responses are distinctive between males of dominant and subordinate social status. Such temporal patterns of transmitter and glucocorticoid activity may reflect neurocircuitry adaptations that result in behavior modified to fit social status.

Evaluation of a pediatric multiple vitamin preparation for total parenteral nutrition in infants and children. I. Blood levels of water-soluble vitamins.

This study represents the first attempt to evaluate the response to the only intravenous vitamin preparation (MVI Pediatric) for infants and children receiving total parenteral nutrition. Eighteen preterm infants (group 1), 26 term infants and children receiving total parenteral nutrition for 2 to 4 weeks (group 2A), and eight infants and children receiving total parenteral nutrition for 3 to 6 months (group 2B) were studied. Term gestation infants and children up to 11 years of age received daily vitamin doses that approximated the 1974 Recommended Dietary Allowances and coincided with the 1975 American Medical Association Nutrition Advisory Group total parenteral nutrition dosage guidelines for children weighing more than 10 kg. Preterm infants received 65% of these dosages. RBC transketolase (vitamin B1), glutathione reductase (B2), and glutamic oxaloacetic transaminase (B6) activities were maintained at normal levels, and niacin levels were maintained within the reference range (7.1 +/- 0.32 micrograms/mL) in all study patients. Pantothenate, biotin, and ascorbate were maintained at reference levels in groups 2A and 2B. In group 1, ascorbic acid was increased significantly during treatment from 1.53 +/- 0.16 to 3.60 by seven days and to 2.54 +/- 0.62 by day 28 of treatment (reference normals = 0.99 +/- 0.1 mg/dL). RBC folate was maintained within the reference range of 411 +/- 76 pg/mL; however, pantothenate and biotin levels increased significantly to more than 2 SD above reference values during treatment, and vitamin B12 levels, which were above the reference range initially, were maintained at more than 2 SD above the reference range throughout treatment. The elevation in vitamin B12 was seen in both group 1 and 2 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoregulation of hepatic glucose production.

In vitro evidence indicates that the liver responds directly to changes in circulating glucose concentrations with reciprocal changes in glucose production and that this autoregulation plays a role in maintenance of normoglycemia. Under in vivo conditions it is difficult to separate the effects of glucose on neural regulation mediated by the central nervous system from its direct effect on the liver. Nevertheless, it is clear that nonhormonal mechanisms can cause significant changes in net hepatic glucose balance. In response to hyperglycemia, net hepatic glucose output can be decreased by as much as 60-90% by nonhormonal mechanisms. Under conditions in which hepatic glycogen stores are high (i.e. the overnight-fasted state), a decrease in the glycogenolytic rate and an increase in the rate of glucose cycling within the liver appear to be the explanation for the decrease in hepatic glucose output seen in response to hyperglycemia. During more prolonged fasting, when glycogen levels are reduced, a decrease in gluconeogenesis may occur as a part of the nonhormonal response to hyperglycemia. A substantial role for hepatic autoregulation in the response to insulin-induced hypoglycemia is most clearly evident in severe hypoglycemia (< or = 2.8 mmol/l). The nonhormonal response to hypoglycemia apparently involves enhancement of both gluconeogenesis and glycogenolysis and is capable of supplying enough glucose to meet at least half of the requirement of the brain. The nonhormonal response can include neural signaling, as well as autoregulation. However, even in the absence of the ability to secrete counterregulatory hormones (glucocorticoids, catecholamines, and glucagon), dogs with denervated livers (to interrupt neural pathways between the liver and brain) were able to respond to hypoglycemia with increases in net hepatic glucose output. Thus, even though the endocrine system provides the primary response to changes in glycemia, autoregulation plays an important adjunctive role.

Insulin- and glucagon-independent effects of calcitonin gene-related peptide in the conscious dog.

Calcitonin gene-related peptide (CGRP) causes vasodilation in many vascular beds, resulting in hypotension and tachycardia. The current studies were conducted in overnight-fasted conscious dogs to determine the effect of different CGRP dosages on carbohydrate metabolism and catecholamine release resulting from hemodynamic changes. During a pancreatic clamp, dogs received intraportal infusions of CGRP at 13, 26, and 52 (n = 3) or 52, 105, and 210 pmol x kg(-1) x min(-1) (n = 4; 60 minutes at each rate). Blood pressure decreased (P < .05) and the heart rate and hepatic blood flow (HBF) increased a maximum of 100% and 30%, respectively (P < .05). For the five CGRP infusion rates, arterial plasma epinephrine increased approximately 1.3-, 2.4-, 7.4-, 12-fold, and eightfold basal, respectively; norepinephrine increased about 2.3-, 3.3-, 4.1-, 4.6-, and 4.8-fold basal, respectively; and cortisol increased about twofold, 3.4-fold, fivefold, sixfold, and 6.2-fold basal, respectively. At CGRP infusion rates of 52 pmol x kg(-1) x min(-1) or higher, increases (P < .05) occurred for plasma glucose, endogenous glucose production (EndoRa), and net hepatic uptake of gluconeogenic substrates (maximum change, 24 mg/dL, 1.3 mg x kg(-1) x min(-1), and 9.9 micromol x kg(-1) x min(-1), respectively). Arterial blood glycerol concentrations increased only a maximum of 30%. At the two highest CGRP infusion rates, glycerol returned to basal concentrations and arterial plasma nonesterified fatty acids (NEFAs) decreased. The increased net hepatic uptake of gluconeogenic substrates during CGRP infusion was sufficient to account for 49% to 58% of the increase in EndoRa. CGRP has no apparent direct effects on hepatic carbohydrate metabolism, but the catecholamines, at levels similar to those observed during CGRP infusion, stimulate hepatic glycogenolysis. Therefore, some factor(s) other than CGRP, probably an increase in circulating catecholamine concentrations, would appear to be responsible for at least 42% to 51% of the increase in EndoRa.

A critical period for the organization of alternative male phenotypes of tree lizards by exogenous testosterone?

Male tree lizards (Urosaurus ornatus) exhibit permanent adult differences in color and size that are functionally linked with behavioral differences: males with a central blue throat patch are territorial, more aggressive, and smaller than males lacking the patch, who are nomads or satellites foregoing territory defense. Gonadectomy or long-lasting hormone implants in hatchlings affect the development of these permanent adult differences, but similar manipulations in adults are ineffective. Analogous early hormone actions in vertebrate sexual differentiation typically must occur during a critical period. Whether there is a critical period for early hormone actions affecting development of male types in tree lizards is unclear. We followed a protocol identical to our previous experiments on hatchlings, but we manipulated testosterone (T) in later-aged juveniles to determine if they remained sensitive to such hormone manipulations. Testosterone implants given at 60 days posthatching (day 60) did not alter adult throat color, indicating that sensitivity of throat color to T declines by day 60. This contrasts to our earlier work where adult color was affected by T manipulations on day 30. However, size and throat color responded differently to exogenous T, as juveniles given T implants at day 60 grew less than control-implanted males.

Neuroendocrine responses in free-living female and male lizards after aggressive interactions.

Although female aggression is found in many species and in a variety of contexts, little is known about its physiological bases. To compare neuroendocrine responses to aggression in females and males, we staged aggressive interactions between free-living territorial mountain spiny lizards and same-sex intruders and measured brain monoamines, plasma steroid hormone levels, and plasma glucose levels. Both females and males that had participated in a staged aggressive interaction had similar changes in serotonin (5-HT) activity in telencephalic tissue punches as indicated by a lowered ratio of forebrain:brainstem 5-HT concentrations. In addition, both females and males had elevated plasma corticosterone (B) after an aggressive interaction when compared to controls. The only difference detected between males and females was that females had a higher ratio of forebrain:brainstem norepinephrine (NE) concentrations throughout the brain compared to males. Together, these data indicate that acute neural and hormonal responses that accompany aggressive interactions in females are similar to those in males.

Sympathetic mediation of stress and aggressive competition: plasma catecholamines in free-living male tree lizards.

The sympathetic nervous system and adrenal catecholaminergic tissue act to prepare an animal for "fight or flight" by release of catecholamines into synapses and plasma. However, few studies have measured plasma catecholamines in nonmammalian vertebrates and none have measured them in free-living animals. We report plasma levels of norepinephrine (NE), epinephrine (EPI) and dopamine (DA) in free-living tree lizards (Urosaurus ornatus) bled in the field: 1) immediately after capture, 2) after 10 minutes of restraint, 3) immediately after a staged territorial encounter and 4) four minutes after the end of a staged territorial encounter. Time to capture and time to bleed after capture were also recorded for each sample. Time to capture had little effect on plasma catecholamines suggesting that plasma catecholamines do not rise during the brief pursuit by the investigator necessary to capture the lizards in the field. In contrast, plasma NE and EPI increased during blood collection. However, this response was very consistent allowing comparisons to be made using analysis of covariance to control for time to bleed. Results indicate that restraint stress caused a large increase in plasma levels of NE, E and DA. Plasma levels of NE and E, but not plasma DA, were also significantly elevated both immediately and 4 minutes after aggressive encounters, although less so than following restraint stress. These studies show that stress and aggression activate the sympatho-adrenal system. This activation could be involved in behavioral changes during aggression, meeting metabolic demands of the encounter, or both.

Adapting the 24-hr. recall for epidemiologic studies of school children.

Chemical analysis of food actually eaten would be the most accurate method for analyzing the diets of children, but this technique is not feasible for most nutrition staffs. An improved 24-hr. dietary recall can be used by a small, well trained staff to collect more reliable data on a large number of school children. Vigilant monitoring of school lunch operations, incorporation of known recipes in the ETNV, and organizing probing techniques are necessary to insure the reliability of the tool. The low coefficients of variation of duplicate recalls noted in the study indicate that the error of measurement between interviewers is small, if the tool is carefully tested and sophisticated before use in the field and if observers are carefully trained by a written protocol.