Decline In Plasma Glucose Concentration Research Articles

Comparison of a modified 2-step insulin response test performed with porcine zinc insulin and an oral glucose test to detect hyperinsulinemic Icelandic horses

Both, oral and intravenous (IV) testing protocols, are recommended and still used to detect insulin dysregulation (ID) in equids. However, IV tests mainly focus on peripheral insulin resistance (IR), while oral tests assess hyperinsulinemia (HI), which are different aspects of ID. The objective of this study was to describe if horses with HI also demonstrate IR and consequently can be detected by a modified 2-step insulin response test (2-step IRT) performed with a veterinary approved porcine zinc insulin (PZI). Twelve Icelandic horses were subjected to an OGT and 2-step IRT in a crossover study. Serum insulin concentrations during the OGT revealed that six horses were hyperinsulinemic (HI) while six were not (NON-HI). To describe the glucose response to IV injected PZI, the decline of plasma glucose concentration within the first 30 min was analyzed. Glucose reduction was similar in horses with and without HI during the 2-step IRT over time. Additionally, none of the horses reached a glucose reduction of ≥ 50% at 30 min. The results of the present study indicated that a comparable insulin mediated glucose uptake may be observed in horses with and without HI during a modified 2-step IRT. While six out of twelve horses were identified as HI by the OGT, all twelve horses were identified as IR by the modified 2-step IRT performed with PZI underlining the importance, but difficulty in choosing the right diagnostic tool in clinical settings to assess ID.

1235-P: A Prospective Characterization of Metabolic and Metabolomic Profiles of COVID-19–Associated New-Onset Diabetes Patients Presenting with DKA from India

Background: Recent evidence suggests a bidirectional relationship between COVID-infection and new-onset diabetes (NOD) presenting with DKA. Methodology: This one-year prospective study comprised of 29 COVID-negative DKA (controls) and 52 COVID-positive-DKA patients (18 NOD, 15 T1DM ,T2DM) . NOD were previously normoglycemic and negative for GAD/IA-2/ZnT8 autoantibodies. After 75g- OGTT with estimation of glucose, C-peptide, FFA and insulin at 0,15, 30,45, 60,90 ,120, 150 and 180minutes, Insulin secretion rate (ISR) [C-peptide-deconvolution] , Hepatic insulin sensitivity [AUC-glucose × AUC-insulin during first 30-minutes of OGTT ], Peripheral insulin sensitivity [ dG/dt ÷ mean plasma insulin concentration; dG/dt rate of decline in plasma glucose concentration]were calculated alongwith Metabolomics and Adipose tissue gene expression. All tests were performed at admission and 4, 8, and 12-months of followup. Results: At baseline, ISR in NOD was significantly reduced than controls (p=0.001) but similar to T1DM (p=0.15) . Nearly 83% (n=17) of NOD with DKA had near-complete recovery of ISR on follow-up compared to T1DM (all p<0.01) ,with non-remitters (n=3) having significantly worse admission Hba1c and IL-6 (all p<0.01) . NOD had significantly increased hepatic and peripheral insulin resistance compared to T1DM (all p<0.05) ,but similar to T2DM (all p>0.05) . Their Metabolomics revealed increased inflammatory phosphatidylcholines, that correlated with peripheral glucose uptake (p<0.01) ,while RNA sequencing showed significantly enhanced WNT5A , TLR4 (Toll-like Receptor-4) and RETN (resistin) than T1DM and T2DM (both p=0.001) . Conclusion: Our study provides novel insights into COVID-associated NOD with DKA. Majority have near-complete recovery of insulin secretion while simultaneous multi-tissue insulin resistance and inflammatory adipose tissue profiles persist as drivers of hyperglycemia . Disclosure R.Dasgupta: None. S.Mondal: None. R.Garai: None. B.Chowdhury: None. A.Hazra: None. M.Lodh: None. A.Ganguly: None.

Levels of personality functioning and not depression predict decline of plasma glucose concentration in patients with type 2 diabetes mellitus

AimsPsychosocial variables influence chronic diseases, such as type 2 diabetes mellitus. While there is evidence for a negative impact of depression, much less is known about stable, personality oriented factors. Aim of the study was to assess the impact of depression and personality functioning on glucose regulation in patients with type 2 diabetes. MethodsSeventy-five adult individuals with a first diagnosis of type 2 diabetes were consecutively recruited in an outpatient medical practice. Plasma glucose (HbA1c) was measured at initial contact, and after three and six months of a standardized disease management program. Depression was assessed by self-report (Patient Health Questionnaire, PHQ-D), levels of personality functioning with the screening version of the Operationalized Psychodynamic Diagnosis structure questionnaire (OPD-SQS). ResultsUsing mixed regression models, OPD-SQS scores were associated with lower baseline levels of HbA1c, but a less steep decline over time. PHQ-D scores were neither associated with intercept nor with slopes of HbA1c. ConclusionsIn type 2 diabetes, levels of personality functioning but not depression predicted decline in plasma glucose during the first six months of a standardized disease management program. Personality functioning may be especially important in chronic diseases that demand a high level of compliance and lifestyle change.

Anti-inflammatory salicylate treatment alters the metabolic adaptations to lactation in dairy cattle

Adapting to the lactating state requires metabolic adjustments in multiple tissues, especially in the dairy cow, which must meet glucose demands that can exceed 5 kg/day in the face of negligible gastrointestinal glucose absorption. These challenges are met through the process of homeorhesis, the alteration of metabolic setpoints to adapt to a shift in physiological state. To investigate the role of inflammation-associated pathways in these homeorhetic adaptations, we treated cows with the nonsteroidal anti-inflammatory drug sodium salicylate (SS) for the first 7 days of lactation. Administration of SS decreased liver TNF-α mRNA and marginally decreased plasma TNF-α concentration, but plasma eicosanoids and liver NF-κB activity were unaltered during treatment. Despite the mild impact on these inflammatory markers, SS clearly altered metabolic function. Plasma glucose concentration was decreased by SS, but this was not explained by a shift in hepatic gluconeogenic gene expression or by altered milk lactose secretion. Insulin concentrations decreased in SS-treated cows on day 7 compared with controls, which was consistent with the decline in plasma glucose concentration. The revised quantitative insulin sensitivity check index (RQUICKI) was then used to assess whether altered insulin sensitivity may have influenced glucose utilization rate with SS. The RQUICKI estimate of insulin sensitivity was significantly elevated by SS on day 7, coincident with the decline in plasma glucose concentration. Salicylate prevented postpartum insulin resistance, likely causing excessive glucose utilization in peripheral tissues and hypoglycemia. These results represent the first evidence that inflammation-associated pathways are involved in homeorhetic adaptations to lactation.

Oxyntomodulin attenuates exendin-4-induced hypoglycemia in cattle

Oxyntomodulin (OXM), glucagon, glucagon-like peptide-1 (GLP-1), and exendin-4 (Ex-4) are peptide hormones that regulate glucose homeostasis in monogastric and ruminant animals. Recently, we reported that the insulin-releasing effects of OXM and glucagon in cattle are mediated through both GLP-1 and glucagon receptors. The purpose of this study was to examine the mechanisms of the glucoregulatory actions induced by Ex-4, GLP-1, OXM, and glucagon and the interrelationships among these hormones in cattle. Two experiments were performed in Holstein cattle. In Experiment 1, we initially assessed the effects of intravenous (iv) bolus injection of 0, 0.25, 1, and 2 μg/kg body weight (BW) of Ex-4, GLP-1, and OXM on insulin and glucose concentrations in 3-mo-old intact male Holstein calves. In Experiment 2, we studied insulin and glucose responses to iv coinjection of 0.25 μg of Ex-4 or GLP-1/kg BW with 2 μg of OXM or glucagon/kg BW in 4-mo-old Holstein steers. Administration of peptides and blood sampling were done via a jugular catheter. Plasma was separated and the concentrations of peptides and glucose in plasma were analyzed using radioimmunoassay and enzymatic methods, respectively. Results showed that the potent glucoregulatory action of Ex-4 in 4-mo-old steers was delayed and attenuated when Ex-4 was coinjected with OXM. The decline in plasma glucose concentrations began at 5 min in the Ex-4-injected group (P < 0.05) vs 15 min in the Ex-4 + OXM–injected group (P < 0.05). Plasma concentrations of glucose at 30 min were reduced 26% from basal concentrations in the Ex-4-injected group and 13% in the Ex-4 + OXM–injected group (P < 0.001). Results also showed that the glucose concentrations initially increased in the Ex-4 + glucagon–treated group, but declined to a relatively hypoglycemic condition by 90 to 120 min. In contrast, the glucose concentrations at specific time points between the GLP-1 + OXM–injected group and the OXM-injected group did not differ. Similarly, the glucose concentrations in the GLP-1 + glucagon–injected group did not differ from those in the glucagon-injected group. Because OXM and glucagon mediate glucose concentrations via the glucagon receptor, it is suggested that the potent glucose-lowering action of Ex-4 might include the glucagon receptor antagonistic action of Ex-4.

Antioxidant defenses and biochemical changes in the neotropical fish pacu, Piaractus mesopotamicus: Responses to single and combined copper and hypercarbia exposure

This study investigated the potentially detrimental effects of copper and elevated aquatic CO2 (hypercarbia), alone or in combination, on pacu, Piaractus mesopotamicus. Fish were exposed for 48h to control (no copper addition in normocarbia), to 400μg Cu2+L−1, to hypercarbic (1% CO2; PCO2=6.9mm Hg) water and to 400μg Cu2+L−1+hypercarbia. In liver the single factors caused an increase in lipid hydroperoxide concentration that was not observed when the factors were combined. Copper exposure elicited increased hepatic superoxide dismutase activity, irrespective of aquatic CO2 level. On the other hand, the effects of copper on hepatic glutathione peroxidase activity were dependent on water CO2 levels. The two stressors combined did not affect hepatic catalase activity. Hypercarbic water caused a decline in plasma glucose concentration, but this was not observed when hypercarbia was combined with copper exposure. Copper caused a decrease in branchial Na+/K+-ATPase activity that was independent of water CO2 level. Copper caused an increase in branchial metallothionein concentration that was independent of water CO2 level. Thus, branchial metallothionein and Na+/K+-ATPase were effective biomarkers of copper exposure that were not affected by water CO2 level.

Role of Sphingolipid Mediator Ceramide in Obesity and Renal Injury in Mice Fed a High-Fat Diet

The present study tested a hypothesis that excess accumulation of sphingolipid, ceramide, its metabolites, or a combination contributes to the development of obesity and associated kidney damage. Liquid chromatography/mass spectrometry analysis demonstrated that C57BL/6J mice on the high-fat diet (HFD) had significantly increased plasma total ceramide levels compared with animals fed a low-fat diet (LFD). Treatment of mice with the acid sphingomyelinase (ASMase) inhibitor amitriptyline significantly attenuated the HFD-induced plasma ceramide levels. Corresponding to increase in plasma ceramide, the HFD significantly increased the body weight gain, plasma leptin concentration, urinary total protein and albumin excretion, glomerular damage index, and adipose tissue ASMase activity compared with the LFD-fed mice. These HFD-induced changes were also significantly attenuated by treatment of mice with amitriptyline. In addition, the decline of plasma glucose concentration after an intraperitoneal injection of insulin (0.15 U/kg b.wt.) was more sustained in mice on the HFD with amitriptyline than on the HFD alone. Intraperitoneal injection of glucose (3 g/kg b.wt.) resulted in a slow increase followed by a rapid decrease in the plasma glucose concentration in LFD and HFD plus amitriptyline-treated mice, but such blood glucose response was not observed in HFD-fed mice. Immunofluorescence analysis demonstrated a decrease in the podocin and an increase in the desmin in the glomeruli of HFD-fed mice compared with the LFD and HFD plus amitriptyline-treated mice. In conclusion, our results reveal a pivotal role for ceramide biosynthesis in obesity, metabolic syndrome, and associated kidney damage.

Enhanced insulin sensitivity of gene-targeted mice lacking functional KCNQ1

The pore-forming K+-channel alpha-subunit KCNQ1 is expressed in a wide variety of tissues including heart, skeletal muscle, liver, and epithelia. Most recent evidence revealed an association of the KCNQ1 gene with the susceptibility to type 2 diabetes. KCNQ1 participates in the regulation of cell volume, which is, in turn, critically important for the regulation of metabolism by insulin. The present study explored the influence of KCNQ1 on insulin-induced cellular K+ uptake and glucose metabolism. Insulin (100 nM)-induced K+ uptake was determined in isolated perfused livers from KCNQ1-deficient mice (kcnq1(-/-)) and their wild-type littermates (kcnq1(+/+)). Moreover, plasma glucose and insulin levels, intraperitoneal glucose (3 g/kg) tolerance, insulin (0.15 U/kg)-induced hypoglycemia, and peripheral uptake of radiolabeled 3H-deoxy-glucose were determined in both genotypes. Insulin-stimulated hepatocellular K+ uptake was significantly more sustained in isolated perfused livers from kcnq1(-/-) mice than from kcnq1(+/+)mice. The decline of plasma glucose concentration following an intraperitoneal injection of insulin was again significantly more sustained in kcnq1(-/-) than in kcnq1(+/+) mice. Both fasted and nonfasted plasma glucose and insulin concentrations were significantly lower in kcnq1(-/-) than in kcnq1(+/+)mice. Following an intraperitoneal glucose injection, the peak plasma glucose concentration was significantly lower in kcnq1(-/-) than in kcnq1(+/+)mice. Uptake of 3H-deoxy-glucose into skeletal muscle, liver, kidney and lung tissue was significantly higher in kcnq1(-/-) than in kcnq1(+/+)mice. In conclusion, KCNQ1 counteracts the stimulation of cellular K+ uptake by insulin and thereby influences K+-dependent insulin signaling on glucose metabolism. The observations indicate that KCNQ1 is a novel molecule affecting insulin sensitivity of glucose metabolism.

Intravenous AICAR administration reduces hepatic glucose output and inhibits whole body lipolysis in type 2 diabetic patients

The 5'-AMP-activated protein kinase (AMPK) pathway is intact in type 2 diabetic patients and is seen as a target for diabetes treatment. In this study, we aimed to assess the impact of the AMPK activator 5-aminoimidazole-4-carboxamide riboside (AICAR) on both glucose and fatty acid metabolism in vivo in type 2 diabetic patients. Stable isotope methodology and blood and muscle biopsy sampling were applied to assess blood glucose and fatty acid kinetics following continuous i.v. infusion of AICAR (0.75 mg kg(-1) min(-1)) and/or NaCl (0.9%) in ten male type 2 diabetic patients (age 64 +/- 2 years; BMI 28 +/- 1 kg/m(2)). Plasma glucose rate of appearance (R (a)) was reduced following AICAR administration, while plasma glucose rate of disappearance (R (d)) was similar in the AICAR and control test. Consequently, blood glucose disposal (R (d) expressed as a percentage of R (a)) was increased following AICAR infusion (p < 0.001). Accordingly, a greater decline in plasma glucose concentration was observed following AICAR infusion (p < 0.001). Plasma NEFA R (a) and R (d) were both significantly reduced in response to AICAR infusion, and were accompanied by a significant decline in plasma NEFA concentration. Although AMPK phosphorylation in skeletal muscle was not increased, we observed a significant increase in acetyl-CoA carboxylase phosphorylation (p < 0.001). The i.v. administration of AICAR reduces hepatic glucose output, thereby lowering blood glucose concentrations in vivo in type 2 diabetic patients. Furthermore, AICAR administration stimulates hepatic fatty acid oxidation and/or inhibits whole body lipolysis, thereby reducing plasma NEFA concentration.

Metabolic Responses to Exercise after Carbohydrate Loads in Healthy Men and Women

This study aimed to investigate gender differences in i) pancreatic insulin secretory (beta-cell sensitivity) and whole body insulin sensitivity responses to an intravenous carbohydrate (CHO) load, and (ii) metabolic responses to exercise after both intravenous and oral CHO loads. Seven untrained healthy men and seven age-, body mass-, and VO2max-matched women performed two trials. In one trial they cycled for 60 min at 50% VO2max, starting 60 min after ingestion of a carbohydrate-rich meal (ME trial). In the other trial, subjects were infused with 20% dextrose solution to maintain blood glucose concentration at approximately 8 mmol x L(-1) for 60 min (INF trial), then the infusion rate was maintained constant during the following 60 min while exercising at 50% VO2max. There was no gender effect on beta-cell sensitivity (serum insulin: 161 +/- 37 and 159 +/- 28 pmol x L(-1) for men and women, respectively) and whole body insulin sensitivity (155 +/- 24 and 135 +/- 29 mg x KgFFM(-1) x min(-1) per pmol x L(-1) x 100 for men and women, respectively). This may explain the similarity in glycemic, substrate oxidation and other metabolic responses to exercise after both intravenous and oral CHO loads in men and women. These results suggest that moderate exercise performed in the postprandial state presents a similar challenge to the ability of healthy, untrained men and women to perform exercise without a substantial decline in plasma glucose concentration below fasting values.

Hypocalcemia Reduces Endogenous Glucose Production in Hyperketonemic Sheep

In previous experiments it has been shown that hyperketonemia lowered plasma glucose concentration in sheep and depressed endogenous glucose production by approximately 30%. This facilitates the onset of pregnancy toxemia. In the last trimester of gestation, hyperketonemia in sheep is often associated with hypocalcemia. There is an indication that hypocalcemia exerts an additional depressive effect on endogenous glucose production. The present study was undertaken to examine the effect in sheep of hypocalcemia on endogenous glucose production in the presence of normo- and hyperketonemia. The experiments were carried out with seven multiparous sheep during three different reproductive states, i.e., during pregnancy (10±8 d prepartum), during lactation (21±8 d postpartum), and 4wk after weaning of the lambs. Concentration of glucose in plasma, turnover of glucose and the rate constant of glucose turnover were measured by isotope dilution during normo- and hypocalcemia and in the presence of normal and elevated β-hydroxybutyrate (BHB) concentrations. Hypocalcemia was induced by i.v. infusions of Na2EDTA. Hyperketonemia was maintained by i.v. infusion of DL-β-hydroxybutyrate. The experiments showed that induction of hypocalcemia: 1) induced a decline in plasma glucose concentration in all reproductive states during normo- and hyperketonemia and 2) significantly lowered endogenous production of glucose in nonpregnant hyperketonemic and in lactating normoketonemic ewes. Pregnant normoketonemic ewes were able to compensate for the hypoglycemic effect of hypocalcemia and to keep endogenous production at the normocalcemic level. We concluded that hypocalcemia does not promote the onset of pregnancy toxemia per se but will facilitate the development of the disease when it is present in combination with hyperketonemia.

Neonatal Care of the Infant of the Diabetic Mother

After completing this article, readers should be able to: 1. Describe the most significant factor influencing neonatal morbidity in the diabetic pregnancy. 2. Characterize the impact of maintaining as normal a metabolic state as possible on the potential for perinatal and neonatal complications. 3. Describe the optimal location and services for delivery of a diabetic parturient. 4. Characterize the evaluation of an infant of a diabetic mother who requires resuscitation after birth. 5. Delineate the factor that most increases the chance of successful management of an infant of a diabetic mother in a regular nursery setting. Although many infants of diabetic mothers (IDMs) have an uneventful perinatal course, there is still an increased risk of complications, even in the infant born to the woman who has gestational diabetes. This discussion highlights specific factors that are critical in the immediate care of the IDM in the delivery room, in the nursery, and after discharge from the hospital. The care of this neonate builds on the pathophysiologic concepts presented in “The Infant of the Diabetic Mother” also appearing in this issue and other recent reviews of the subject. (1)(2) The physician responsible for the care and delivery of the parturient must inform the neonatologist, pediatrician, or their designee responsible for the care of the neonate of the mother’s condition well in advance of delivery to ensure optimal care of the newborn. Among the specific factors that are of utmost importance are the type of diabetes and degree of maternal control, prior pregnancy history, and complications occurring during the pregnancy, including data about fetal monitoring for determination of fetal size and maturation. This information allows the physician caring for the neonate to anticipate many, if not most, of the potential fetal and neonatal complications and assist in determining if a neonatologist needs to be present …

Role for the pineal and melatonin in glucose homeostasis: pinealectomy increases night-time glucose concentrations.

The effects of melatonin on glucose metabolism are far from understood. In rats, the biological clock generates a 24-h rhythm in plasma glucose concentrations, with declining concentrations in the dark period. We hypothesized that, in the rat, melatonin enhances the dark signal of the biological clock, decreasing glucose concentrations in the dark period. We measured 24-h rhythms of plasma concentrations of glucose and insulin in pinealectomized rats fed ad libitum and subjected to a scheduled feeding regimen with six meals equally distributed over the light/dark cycle and compared them with previous data of intact rats. Pinealectomy dampened the amplitude of the 24-h rhythm in plasma glucose concentrations in rats fed ad libitum, and abolished it completely in rats subjected to the scheduled feeding regimen, while plasma insulin concentrations did not change under both conditions. Pinealectomy abolished the nocturnal decline in plasma glucose concentrations irrespective of whether rats were fed ad libitum or subjected to the scheduled feeding regimen. Melatonin replacement restored 24-h mean plasma glucose concentrations in pinealectomized rats that were subjected to the scheduled feeding regimen but, interestingly, it did not restore the 24-h rhythm. Melatonin treatment also resulted in higher meal-induced insulin responses, probably mediated via an increased sensitivity of the beta-cells. Taken together, our data demonstrate that the pineal hormone, melatonin, influences both glucose metabolism and insulin secretion from the pancreatic beta-cell. The present study also demonstrates that removal of the pineal gland cannot be compensated by mimicking plasma melatonin concentrations only.

Masoprocol (nordihydroguaiaretic acid): a new antihyperglycemic agent isolated from the creosote bush (Larrea tridentata).

An ethnomedically-driven approach was used to evaluate the ability of a pure compound isolated from the creosote bush (Larrea tridentata) to lower plasma glucose concentration in two mouse models of type 2 diabetes. The results indicated that plasma glucose concentration fell approximately 8 mmol/l in male C57BL/ks-db/db or C57BL/6J-ob/ob mice following the oral administration of masoprocol (nordihydroguaiaretic acid), a well known lipoxygenase inhibitor. The decline in plasma glucose concentration following masoprocol treatment in the mice was achieved without any change in plasma insulin concentration. In addition, oral glucose tolerance improved and the ability of insulin to lower plasma glucose concentrations was accentuated in masoprocol-treated db/db mice. These data raise the possibility that masoprocol, or other lipoxygenase inhibitors, represents a new approach to the pharmacological treatment of Type 2 diabetes.

Effect of hepatic vagotomy on plasma insulin levels during fasting in rats

The present investigation was designed to evaluate the effect of a selective hepatic vagotomy (HV) on the insulin response in rats fasted for 24 h when blood glucose levels were or were not maintained by a constant glucose infusion. Rats were divided into three dietary groups: one group of normally fed rats, one group of 24-h fasted rats, and one group of 24-h fasted rats infused with glucose throughout the fasting period. Each one of these groups was subdivided into HV and sham-operated (SHM) rats. Fasting without glucose infusion resulted in a significant ( p < 0.05) decrease in plasma glucose, liver glycogen, and insulin concentrations and in a significant ( p < 0.05) increase in β-hydroxybutyrate and FFA concentrations. Despite the maintenance of plasma glucose concentrations in the glucose-infused groups, the concentrations of liver glycogen and insulin were still decreased ( p < 0.01) and the concentrations of β-hydroxybutyrate were still increased ( p < 0.05) at the end of the fasting period. However, no significant differences in insulin or in β-hydroxybutyrate concentrations were found between HV and SHM rats. It is concluded that the decline in plasma glucose concentration during fasting does not totally explain the insulinopenic response to fasting, and that the liver, through the mediation of the hepatic vagus nerve does not seem to contribute to insulinopenia in 24-h fasted rats.

Sex differences in the adaptation of glucose metabolism to short-term fasting: Effects of oral contraceptives

The adaptation to long-term starvation is different in men and women. To evaluate whether there are also sex differences during short-term fasting (<24 hours), we studied glucose metabolism after 16 and again after 22 hours of starvation in healthy subjects: six men, six women in both the follicular and luteal phases of their menstrual cycle, and six women on oral contraceptives ([OCC] day 12 of cycle). Glucose oxidation was measured by indirect calorimetry, and hepatic glucose output by infusion of 3- 3H-glucose. There were no differences in hepatic glucose output between men and women during short-term fasting. The basal (16 hours) plasma glucose concentration was lower in women on OCC than in men ( P < .05). Prolongation of the postabsorptive state induced a similar decline in plasma glucose concentrations in all groups. Basal (16 hours) glucose oxidation was lower in women on OCC than in men ( P < .05). Prolongation of the postabsorptive state by 6 hours caused a significant decrease in glucose oxidation only in men. After 22 hours of fasting, glucose oxidation was lower in women on OCC than in women with normal menstrual cycles. In conclusion, the metabolic adaptation to the postabsorptive state (<24 hours of fasting) is regulated differently in women on OCC as compared with women with normal menstrual cycles and men. These differences preclude inclusion of women on OCC in studies of glucose metabolism in the postabsorptive state.

Exercise metabolism at different time intervals after a meal

To determine how long a meal will affect the metabolic response to exercise, nine endurance-trained and nine untrained subjects cycled for 30 min at 70% of peak O2 consumption (VO2 peak) 2, 4, 6, 8, and 12 h after eating 2 g carbohydrate/kg body wt. In addition, each subject completed 30 min of cycling 4 h after the meal at an intensity that elicited a respiratory exchange ratio (RER) of 0.94-0.95. During exercise after 2 and 4 h of fasting, carbohydrate oxidation was elevated 13-15% compared with the response to exercise after an 8- and 12-h fast (P less than 0.01). The increase in blood glycerol concentration during exercise (30 to 0 min) was linearly related to the length of fasting (r = 0.99; P less than 0.01). In all subjects, plasma glucose concentration declined 17-21% during exercise after 2 h of fasting (P less than 0.01). Plasma glucose concentration also declined (15-25%) during exercise in the trained subjects after 4 and 6 h of fasting (P less than 0.05) but did not change in the untrained subjects. However, the decline in plasma glucose concentration was similar (14%) in the two groups when the exercise intensity was increased in the trained subjects (i.e., 78 +/- 1% VO2 peak) and decreased in the untrained subjects (i.e., 65 +/- 3% VO2 peak) to elicit a similar RER.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood glucose prior to meal request in humans isolated from all temporal cues

The factors responsible for meal initiation in man are not known. Recently, a small, transient decline in blood glucose was found to precede meals in freely feeding rats (1). To determine whether a similar decline in blood glucose precedes meals in humans, we measured plasma glucose concentration before and after requests for lunch on 4 different days in each of 7 subjects living in a setting that eliminated temporal cues and most or all external prompts for eating. Under these conditions, subjects could request any meal at any time by naming it and specifying its content. Meals were promptly prepared and served. Blood was sampled at randomized intervals averaging 20 minutes. Blood samples from 120 minutes preceding the subject's request for lunch to 90 minutes after the request were analyzed for glucose by the hexokinase method. The mean plasma glucose concentration did not change significantly from about 1 hour before lunch request to 20–30 minutes after the request. A transient decline in glucose similar to that reported in the rat was observed prior to only 1 of the 28 lunches. Given the ease of obtaining food and the absence of the usual temporal and psychosocial cues for eating, the results are not consistent with the hypothesis that meal requests in humans are triggered by a transient decline of plasma glucose concentration. The hypothesis is not disproven, however, since the intersample intervals of about 20 minutes may have failed to detect decreases of blood glucose that were smaller or of shorter duration than those of the rat.

Hypoglycemia Enhances Turnover of Corticotropin-Releasing Factor and of Vasopressin in the Zona Externa of the Rat Median Eminence*

Insulin administration to overnight fasted rats causes a dose-dependent decline in plasma glucose concentrations and a dose-dependent increase in plasma ACTH concentrations. The ACTH response, but not the glucose response, was blocked by treatment with chlorpromazine-morphine-pentobarbital, indicating that the main factors triggering the ACTH response are of central, rather than peripheral, origin. To study whether insulin affected the turnover of CRF and vasopressin (AVP) in the zona externa of the median eminence (ZEME), we determined the rate of decline of both hypophysiotropic factors in rats with or without blockade of axonal transport by colchicine. In the ZEME, the concentrations of CRF and AVP were assessed by quantitative immunocytochemistry (QICC) in tissue sections or by RIA in median eminence extracts. QICC allows selective quantification of AVP and other peptides within the ZEME. The changes in the CRF content, as measured by QICC and RIA, were linearly correlated (r = 0.99), demonstrating that changes in peptide-staining intensity reflect changes in peptide content. Colchicine, when given intracisternally in a nontoxic dose of 5 micrograms, had no marked effect on resting plasma levels of ACTH and only slightly reduced the ACTH response to insulin-induced hypoglycemia. In the ZEME, CRF and AVP concentrations at rest were not affected by colchicine. In colchicine-treated rats insulin-induced hypoglycemia resulted in a prominent decline in CRF and AVP concentrations in the ZEME. The CRF concentration declined at a rate of 23%/h over a period of 3 h. The AVP concentration declined to a similar extent as CRF over the first hour, but tended to fall at the later time points. We conclude that hypoglycemia increases turnover of both CRF and AVP in the ZEME. However, the turnover rates of both hypophysiotropic peptides do not appear to be quantitatively coupled.

Metabolic effects of low-dose insulin therapy on glucose metabolism in diabetic ketoacidosis.

The effect of low-dose insulin treatment (5-10 U/h) on hepatic glucose production (HGP) and peripheral glucose disposal was determined in 5 insulin-dependent diabetes mellitus (IDDM) subjects who were admitted with diabetic ketoacidosis (DKA; plasma glucose 598 +/- 50 mg/dl, blood pH 7.20 +/- 0.06, plasma bicarbonate 12 +/- 2 meq/L). Basal hepatic glucose production (4.3 +/- 0.5 mg.kg-1.min-1) in the DKA patients was 1.5- to 2-fold greater (P less than .01) than in controls (2.1 +/- 0.1 mg.kg-1.min-1) and nonketotic IDDM subjects (2.9 +/- 0.3 mg.kg-1.min-1), whereas tissue glucose disposal was significantly reduced (1.7 +/- 0.1 vs. 2.1 +/- 0.1 mg.kg-1.min-1, P less than .05). After the institution of insulin therapy (1 mU.kg-1.min-1), the plasma glucose concentration fell at the rate of 60 +/- 5 mg.dl-1.h-1 to reach a value of 220 +/- 10 mg/dl, which was maintained constant for 2 h (insulin-clamp technique). Blood pH (7.21 +/- 0.06 to 7.35 +/- 0.05) and plasma bicarbonate (12 +/- 3 to 18 +/- 2 meq/L) both increased during insulin therapy (P less than .01). The decline in plasma glucose concentration during insulin therapy primarily resulted from a suppression of HGP (from 4.3 +/- 0.5 to 1.7 +/- 0.2 mg.kg-1.min-1, P less than .01) and to a lesser extent from the stimulation of tissue glucose disposal (1.7 +/- 0.2 to 2.6 +/- 0.3 mg.kg-1.min-1, P less than .01). At this time, urine glucose excretion decreased from 2.6 +/- 0.2 to 0.6 +/- 0.1 mg.kg-1.min-1.(ABSTRACT TRUNCATED AT 250 WORDS)