Oral Protein Load Research Articles

Renal response to an oral protein load in patients with central diabetes insipidus before and after treatment with vasopressin.

Different factors have been hypothesized to play a role in the cascade of events associated with the protein-induced glomerular response. However, scant data are available on the possible functional effect of vasopressin (VP) on the glomerular filtration rate (GFR) in humans with central diabetes insipidus (CDI), which was the aim of the present study. Renal function was studied under fasting conditions (baseline) and after a meat meal in 16 patients with CDI before and after treatment with desmopressin (DDAVP) and in 16 control subjects. GFR was measured by the inulin method. At baseline, the GFR was lower in patients with CDI. Treatment with DDAVP resulted in an insignificant increase in GFR, which was not statistically different from untreated patients. After an acute oral protein load, the GFR increased, peaking at 45min post meal in controls, and at 135min post meal in treated and untreated CDI patients. After a meat meal, the peak GFR response is delayed in CDI patients suggesting that VP might indirectly affect tubule-glomerular feedback.

Renal functional reserve

Serum creatinine and glomerular filtration rate (GFR) are the current standard tests tomeasure kidney function. The baseline GFR does not reflect full function of the kidney sincehuman kidneys do not always work at full capacity. Similarly, serum creatinine is not a sensitivemeasure for kidney function or injury. In healthy individuals the GFR physiologically increasesin response to certain stresses or stimuli, such as protein loading.Renal functional reserve (RFR) is defined as the difference between the maximalglomerular filtration rate (generally determined after oral or intravenous protein loading) and thebaseline glomerular filtration rate. The absence of a normal RFR can help identify patients whoare more susceptible to kidney injury. The RFR is also important in patients who develop acutekidney injury and chronic kidney disease. Even though the GFR might return to a baselinelevel, there may be some loss of RFR which can make the patient more susceptible to anotherepisode of kidney injury.Acute kidney injury and chronic kidney disease are considered interconnected syndromes;each is a risk factor for the other. There are no current recommendations regarding theperformance of routine determinations of RFR. Physicians should focus on clinical history andphysical examination in patients with a history of prior episodes of acute kidney injury, monitorrenal function, and avoid nephrotoxic insults.

Persistent decrease of renal functional reserve in patients after cardiac surgery-associated acute kidney injury despite clinical recovery.

Cardiac surgery is a leading cause of acute kidney injury (AKI). Such AKI patients may develop progressive chronic kidney disease (CKD). Others, who appear to have sustained no permanent loss of function (normal serum creatinine), may still lose renal functional reserve (RFR). We extended the follow-up in the observational 'Preoperative RFR Predicts Risk of AKI after Cardiac Surgery' study from hospital discharge to 3 months after surgery for 86 (78.2%) patients with normal baseline estimated glomerular filtration rate (eGFR), and re-measured RFR with a high oral protein load. The primary study endpoint was change in RFR. Study registration at clinicaltrials.gov Identifier: NCT03092947, ISRCTN Registry: ISRCTN16109759. At 3 months, three patients developed new CKD. All remaining patients continued to have a normal eGFR (93.3 ± 15.1 mL/min/1.73 m2). However, when stratified by post-operative AKI and cell cycle arrest (CCA) biomarkers, AKI patients displayed a significant decrease in RFR {from 14.4 [interquartile range (IQR) 9.5 - 24.3] to 9.1 (IQR 7.1 - 12.5) mL/min/1.73 m2; P < 0.001} and patients without AKI but with positive post-operative CCA biomarkers also experienced a similar decrease of RFR [from 26.7 (IQR 22.9 - 31.5) to 19.7 (IQR 15.8 - 22.8) mL/min/1.73 m2; P < 0.001]. In contrast, patients with neither clinical AKI nor positive biomarkers had no such decrease of RFR. Finally, of the three patients who developed new CKD, two sustained AKI and one had positive CCA biomarkers but without AKI. Among elective cardiac surgery patients, AKI or elevated post-operative CCA biomarkers were associated with decreased RFR at 3 months despite normalization of serum creatinine. Larger prospective studies to validate the use of RFR to assess renal recovery in combination with biochemical biomarkers are warranted.

Preoperative Renal Functional Reserve Predicts Risk of Acute Kidney Injury After Cardiac Operation

Although acute kidney injury (AKI) frequently complicates cardiac operations, methods to determine AKI risk in patients without underlying kidney disease are lacking. Renal functional reserve (RFR) can be used to measure the capacity of the kidney to increase glomerular filtration rate under conditions of physiologic stress and may serve as a functional marker that assesses susceptibility to injury. We sought to determine whether preoperative RFR predicts postoperative AKI. We enrolled 110 patients with normal resting glomerular filtration rates undergoing elective cardiac operation. Preoperative RFR was measured by using a high oral protein load test. The primary end point was the ability of preoperative RFR to predict AKI within 7 days of operation. Secondary end points included the ability of a risk prediction model, including demographic and comorbidity covariates, RFR, and intraoperative variables to predict AKI, and the ability of postoperative cell cycle arrest markers at various times to predict AKI. AKI occurred in 15 patients (13.6%). Preoperative RFR was lower in patients who experienced AKI (p< 0.001) and predicted AKI with an area under thereceiver operating characteristic curve (AUC) of 0.83 (95% confidence interval [CI]: 0.70 to 0.96). Patients with preoperative RFRs not greater than 15 mL · min-1 · 1.73 m-2 were 11.8 times more likely to experience AKI (95% CI: 4.62 to 29.89 times, p < 0.001). In addition, immediate postoperative cell cycle arrest biomarkers predicted AKI with an AUC of 0.87. Among elective cardiac surgical patients with normal resting glomerular filtration rates, preoperative RFR was highly predictive of AKI. A reduced RFR appears to be a novel risk factor for AKI, and measurement of RFR preoperatively can identify patients who are likely to benefit from preventive measures or to select for use of biomarkers for early detection. Larger prospective studies to validate the use of RFR in strategies to prevent AKI are warranted. ClinicalTrials.gov identifier: NCT03092947, ISRCTN Registry: ISRCTN16109759.

The role of renal response to amino acid infusion and oral protein load in normal kidneys and kidney with acute and chronic disease.

High protein intake and hyperfiltration have been a focus of major interest as potential mechanism(s) of progression of renal disease. This review will examine: the renal response to a protein meal or amino acid infusion and its use to test the renal functional reserve (RFR); new methods to evaluate RFR; the use of RFR in various pathophysiologic conditions. The renal response to protein/amino acid infusion involves several mechanisms, including nitric oxide, insulin, glucagon, arginine vasopressin, urea, the renal N-Methyl-D-Aspartate Glutamate receptor and modulation of the activity of the tubuloglomerular feedback system. Dose-response studies to evaluate RFR suggest the presence of a potential ceiling. The utilization of a noninvasive technique such as Doppler ultrasonography is trying to simplify the measurement of RFR and to bring this test into different clinical settings. There is increased interest in the presence or absence of RFR in patients with acute kidney injury, hypertension, chronic kidney disease, and its potential long-term implication regarding renal function. The renal response to protein may help us understand the relationship between hyperfiltration, progression of renal disease, and other conditions (overall mortality, cardiovascular complications, and so on) currently being explored.

Renal functional reserve in children with a solitary functioning kidney and chronic kidney disease

O bjective – To examine renal functional reserve (RFR) and blood pressure (BP) in children with a solitary functioning kidney (SFK) and stage 1-3 chronic kidney disease (CKD). M ethod – RFR was measured in 48 children with SFK and in 10 healthy children, as the difference between unstimulated and stimulated clearance of endogenous creatinine by a meat-free oral protein load (OPL). Cimetidine was given 48 h prior to the measurement when the study subjects were on a diet free of meat, fish and poultry. Serum cystatin C and urinary protein (UPRT)/urinary creatinine (UCr) were examined before and 2 hours after OPL. BP was determined by office and by 24-h ambulatory BP monitoring (ABPM). R esults – The majority of the patients (79.6%) had congenital SFK, while the remaining had acquired SFK due to unilateral nephrectomy. Sixteen patients had CKD1, 19 patients had CKD2 and 13 had CKD3. The patients and controls did not differ in terms of age, gender, body size, office and 24-h blood pressure readings and basal GFR. Kidney size was greater and serum cystatin C was higher in patients than in controls. Increased proteinuria and arterial hypertension were found in 24.3% and 18.9% of the patients, respectively. Nocturnal hypertension was more common than that during the daytime. After OPL, GFR significantly increased, more in controls than in patients. Among the patients, the RFR was the highest in the CKD3 group. Conclusion – OPL induced an increase in GFR above its basal value. This response was higher in healthy children than in those with SFK. The positive relationship between RFR and CKD stage and the highest RFR in CKD3 patients suggests well preserved renal functional reserve in patients with moderate renal failure. ABPM is necessary for BP evaluation in children with SFK.

Rationale for the Evaluation of Renal Functional Reserve in Living Kidney Donors and Recipients: A Pilot Study

Background: In living kidney transplantation, preoperative donors' renal functional reserve (RFR) may correlate with postoperative residual renal function in both donors and recipients. The aim of this study was to evaluate the donors' RFR before transplantation and to compare basal and stress renal function before and after transplantation in both donors and recipients. Methods: Seven pairs of living kidney donors and recipients were considered for this observational study. RFR was measured with a renal stress test (RST) before and after the kidney transplantation through an oral protein loading test (1 g/kg of body weight). RFR was defined as the difference between the maximum value of creatinine clearance after protein load (stress glomerular filtration rate, sGFR) and baseline creatinine clearance (basal GFR, bGFR). Results: Before transplantation, a significant difference between sGFR and bGFR (p = 0.04) was observed in donors, with an RFR = 30.6 (11.9-41.5) mL/min/1.73 m². After kidney transplantation, sGFR was similar to bGFR for both donors and recipients (p = 0.13), with a limited RFR (7.9 [6.70-19.25] and 14.90 [-6.67 to 25.53] mL/min/1.73 m², respectively). The sum of the donor's and recipient's post-transplant sGFR was similar to the pre-transplant donor's sGFR (p = 0.73). Conclusion: RST is a safe, feasible, easy, and an inexpensive tool that is able to quantify RFR. In living kidney transplantation, it can be used in clinical practice to measure the original global filtration capacity of the donor's kidneys (sGFR) and to quantify the susceptibility of donors and recipients in developing postoperative kidney dysfunction. However, further studies with an adequate sample size and follow-up period are needed to test this hypothesis.

Doppler ultrasound measurements of renal functional reserve in healthy subjects.

The aim of this study was to calculate the normal values of renal functional reserve in healthy individuals measuring the resistive index and pulsatility index using Doppler ultrasonography. Forty healthy volunteer adults were included in the study. Their basal resistive index and pulsatility index values were measured and after oral protein load at 30th, 75th and 120th minutes, resistive index and pulsatility index measurements were repeated. The maximum changes in resistive index and pulsatility index from baseline were calculated in each subject which represented the renal functional reserve. The mean values of resistive index and pulsatility index decreased significantly starting with 30 minutes and consecutively at 75 and 120 minutes (for all p<0.05). The highest decrease compared to baseline values was recorded at 75 minutes and renal functional reserve values were calculated as 22.2% for resistive index and 25.4% for pulsatility index. Renal functional reserve can be calculated through Doppler resistive index and pulsatility index measures. We consider that it may be helpful to know normal values of renal functional reserve in healthy subjects.

Acute load-dependent effects of oral whey protein on gastric emptying, gut hormone release, glycemia, appetite, and energy intake in healthy men

In healthy individuals, intraduodenal whey protein load-dependently modulates gastrointestinal motor and hormonal functions and suppresses energy intake. The effect of oral whey, particularly the impact of load, has not been evaluated. The purpose of this study was to quantify gastric emptying of 30 and 70 g of oral whey protein loads and their relation to gastrointestinal hormone, glycemic, and appetitive responses. On 3 separate occasions in a randomized, double-blind order, 18 lean men [mean ± SEM age: 24.8 ± 1.4 y; body mass index (in kg/m(2)): 21.6 ± 0.5] received iso-osmolar, equally palatable drinks (∼450 mL) containing 30 g pure whey protein isolate (L), 70 g pure whey protein isolate (H), or saline (control). Gastric emptying (with the use of 3-dimensional ultrasound), plasma cholecystokinin, glucagon-like peptide 1, glucose-dependent insulinotropic peptide, insulin, glucagon, total amino acids, and blood glucose were measured for 180 min after consumption of the drinks, and energy intake at a buffet-style lunch was quantified. Gastric emptying of the L and H drinks was comparable when expressed in kilocalories per minute (L: 2.6 ± 0.2 kcal/min; H: 2.9 ± 0.3 kcal/min) and related between individuals (r = 0.54, P < 0.01). Gastrointestinal hormone, insulin, and glucagon responses to the L and H drinks were comparable until ∼45-60 min after ingestion, after which time the responses became more differentiated. Blood glucose was modestly reduced after the H drink between t = 45 and 150 min when compared with the L drink (all P < 0.05). Energy intake was suppressed by both L and H drinks compared with control (P < 0.05) (control: 1174 ± 91 kcal; L: 1027 ± 81 kcal; and H: 997 ± 71 kcal). These findings indicate that, in healthy lean men, the rate of gastric emptying of whey protein is independent of load and determines the initial gastrointestinal hormone response. This study was registered at www.anzctr.org.au as 12611000706976.

Doppler spectrum of intrarenal blood flow and circadian blood pressure rhythm in hypertensive patients

The aim of the study was to assess relationship of results of 24-h ambulatory blood pressure (24-h ABPM) monitoring on the parameters of renal hemodynamic in hypertensive patients. The renal hemodynamic was evaluated by ultrasound Doppler. The glomerular filtration rate (on a clearance of endogenous creatinine) has been measured out before and after the acute oral protein loading for evaluation of renal functional reserve. The results of one-way ANOVA showed, that the «blood pressure load index» – areas under systolic and diastolic blood pressure curves and systolic and diastolic blood pressure-time index 24 h' influenced extremely negatively on renal pulsating index. These data and their values of 24-h ABPM may be useful for the clinical assessment of hypertensive patient by identifying those at high risk for the presence of renal injury.

Utilidad clínica de la reserva funcional renal

Renal function reserve (RFR) represents the capacity of the kidney to increase glomerular filtration rate (GFR) in response to certain physiological or pathological stimuli or conditions.Baseline GFR displays variable values according to the diet or other factors, and may be normal even when there is an important lowering of nephron number. Once baseline GFR is determined, RFR can be assessed clinically by oral protein load or intravenous aminoacid infusion.RFR is the difference between peak (stress-induced) GFR and basal GFR. In clinical scenarios where hyper-filtration is present (high baseline GFR due to pregnancy, hypertensive or diabetic nephropathy, solitary kidney or kidney donors) RFR may be fully or partially used to achieve normal or supra-normal renal function.RFR test may represent a sensitive and early way to asses kidney functional decline and recovery. In cases of healing with a defect and fibrosis, clinical assessment may suggest a complete recovery, but a reduced RFR may be a sign of a maladaptive repair or sub-clinical loss of renal mass. Therefore, a reduction of RFR may represent the equivalent of renal frailty or susceptibility to insults. The main aim of this article is to review the concept of RFR, its utility in different clinical scenarios and future perspective for its use.

Abnormal Renal Resistive Index in Patients with Mild-to-moderate Chronic Obstructive Pulmonary Disease

Background: Arterial rigidity and endothelial dysfunction are systemic manifestations of chronic obstructive pulmonary disease (COPD). The decrease in renal vascular resistance in order to adapt the increase in glomerular filtration rate after oral protein loading is known as normal renal functional reserve. We tested the hypothesis that COPD patients, even in those with mild-to-moderate airflow obstruction, are affected by systemic inflammation associated with abnormal renal functional reserve. Materials and Methods: The study enrolled 24 current smokers with a cigarette smoking history ^25 pack-years and 8 nonsmokers with normal spirometry as control. Doppler sonography detected the renal resistive index (RRI) before and after oral protein loading to determine the renal functional reserve. Pulmonary function and serum tumor necrosis factor 〈 (TNF-〈) levels were analyzed to compare with the renal functional reserve. Results: The smokers were stratified into 3 groups (Group 1: smokers with normal spirometry, Group 2: mild COPD, Group 3: moderate COPD); nonsmokers as Group 4. The baseline RRI levels were similar in Group 1 and Group 4. After protein loading, the RRI elevated in all smoking groups; moreover, Group 3 had the highest RRI and with longer duration than other groups. The smokers with higher serum TNF-〈 levels had a longer RRI elevation. Multiple linear regression revealed forced expiratory volume in one second (FEV1), serum TNF-〈 levels and aging were independently predictive factors of impaired renal functional reserve. Conclusions: A greater impairment in renal functional reserve of COPD patients was correlated with more severe airway obstruction and inflammation.

Renal functional reserve in children with apparently normal congenital solitary functioning kidney

ObjectiveThe aim of the study was to investigate renal functional reserve (RFR) and to assess its relationship with serum cystatin C and blood pressure in children with apparently normal congenital solitary functioning kidney (SFK). Material and methodsRFR was obtained from the difference of endogenous creatinine clearance (CrCs) before and after a meat-free oral protein load (OPL) in the patients who were pre-treated with cimetidine. Serum cystatin C and urinary protein excretion were determined before and after OPL. ResultsAmong 22 patients (13 boys), aged 9.5±4.3years, 72.7% had increased serum cystatin C, and 54.5% had decreased RFR. Following OPL, CrCs and urine creatinine increased, while serum creatinine and cystatin C remained unchanged. The multiple regression analysis demonstrated that cystatin C could predict more than 90% of RFR variability. ConclusionHalf of the patients with apparently normal SFK had decreased RFR. Serum cystatin C is one of the best predictors of RFR.

Renal reserve in the oldest old

Decline in glomerular filtration rate (GFR) is one of several changes in renal physiology in the elderly. Renal reserve (RR) is the kidney's capacity to increase its basal GFR by at least 20% after a protein overload. Even though it has already been reported that RR is preserved in healthy old people, there is no information whether RR is also preserved in the healthy very old one (older than 74 of age), which we decided to study and report our findings in this paper. We studied RR in 16 healthy persons divided into three age groups: young: 20-40years old (n: 5): 64-74years old (n: 6) and oldest old: >74years old (n: 5). Renal reserve test was performed by assessing creatinine clearance with cimetidine before and after an oral protein load. Statistical analysis was performed using ANOVA test. Even though renal reserve response was present in all age groups, its magnitude (delta GFR) was significantly higher in the healthy young group (103.6±53ml/min) compared to the old one (34.1±40ml/min) (P=0.002), while it was significantly lower in the healthy oldest old (20.7±0.7ml/min) group compared to the other two groups (P=0.002). Renal reserve is preserved in healthy very old people, but its magnitude decreases significantly with age.

Remittent hyperammonemia in congenital portosystemic shunt

Congenital portosystemic shunts (PSS) are rare vascular anomalies with different gross anatomy. Persistent patent ductus venosus (PDV) represents an uncommon cause of intrahepatic PSS. The diagnosis of this condition may not be obvious because of its wide spectrum of clinical manifestations, ranging from asymptomatic to life-threatening disease. We report the case of three boys with neuropsychological symptoms associated with mild fasting hyperammonemia. An oral protein load allowed the detection of a detoxication defect due to PSS related to PDV. This simple procedure can be worthwhile of attention in patients with mental retardation, behavior disturbances, and learning difficulties after exclusion of common causes of inherited hyperammonemia, namely, urea cycle disorders, organic acidemias, and fatty acid oxidation defects.

Renal Function Reserve in Chronic Obstructive Pulmonary Disease with Type II Respiratory Failure

Background and objective: increase in renal blood flow in response to certain stimuli such as dopamine infusion, oral protein load, and amino acid infusion. Reduced or absent renal functional reserve (RFR) is an early index of renal impairment. Our work studies the (RFR) in Chronic Obstructive Pulmonary Disease (COPD) patients with chronic compensated type II respiratory failure. Methods: Our study included 15 COPD patients with compensated type II respiratory failure and 5 normal controls. The patient group had mean Pa O2 56.5±6.4 and Pa CO2 56.5±3.2, while in normal controls the mean Pa O2 was 97.4 ± o.3 and Pa CO2 was 42.3 ± 1.2. Hypoxic patients (Pa O2 or=60mmHgandSaO2 >or=90%withoutriseofPaCO2within2 hours before and during the study. The pulsatility index (PI), an index of reno-vascular resistance (RVR), was measured non invasively by Doppler Ultrasonograghy at baseline and 20 minutes after infusion of dopamine in diuretic dose. Results: The baseline PI was nearly similar in the control group and in COPD patients (no significant difference), the PI fell significantly in the control group after dopamine infusion from 1.03 ± 0.14 to 0.83 ± 0.1(P< 0.05), but increased significantly in COPD patients from 1.02 ± 0.12 to1.18 ± 0.13 (P<0.05) after dopamine infusion. Conclusion: Renal functional reserve is impaired in hypercapnic COPD patients and this may be a factor in the development of edema frequently seen in these patients.

Renal Function Reserve in Chronic Obstructive Pulmonary Disease with Type II Respiratory Failure

increase in renal blood flow in response to certain stimuli such as dopamine infusion, oral protein load, and amino acid infusion. Reduced or absent renal functional reserve (RFR) is an early index of renal impairment. Our work studies the (RFR) in Chronic Obstructive Pulmonary Disease (COPD) patients with chronic compensated type II respiratory failure.

Renal functional reserve in obesity hypertension

The capacity to increase glomerular filtration rate in response to an acute oral protein load is known as the renal functional reserve; the loss of such capacity is used as a marker of hyperfiltration. This physiological response in obese hypertensives is not yet fully understood. We aimed to study the interdependent effects of obesity and hypertension on renal reserve, taking into account renal kallikrein and nitric oxide in the modulation of that parameter. Fourteen obese hypertensives (mean age, 50.5 +/- 0.9 years) and nine lean hypertensives (mean age, 50.6 +/- 2.7 years) were evaluated. Renal haemodynamics and the levels of serum nitric oxide and urinary kallikrein were assessed at baseline and after a protein load (1 g/kg of body weight). An increase in the following parameters was observed when comparing obese and lean hypertensives: basal glomerular filtration rate; renal plasma flow; and urinary kallikrein and nitric oxide levels (129.2 +/- 2.9 vs. 101.4 +/- 3.4 ml/min/1.73 m2; 587.5 +/- 18.2 vs. 502.8 +/- 16.7 ml/min/1.73 m2; 0.120 +/- 0.02 vs. 0.113 +/- 0.02 mU/ml; 23.2 +/- 0.8 vs. 19.5 +/- 1.2 mmol/ml, respectively). The renal reserve was lower in obese hypertensives when compared with that of lean hypertensives (4.1 +/- 0.5 vs. 11.8 +/- 0.8 ml/min, p < 0.005). After a protein load, contrasting with the lean group, inability to elevate the nitric oxide serum levels and a lower increase in urinary kallikrein were observed in the obese group. These data suggest that obese hypertensives lose renal reserve earlier in the evolution to renal dysfunction. This may be due to the defective modulation of renal vasodilatation mechanisms by renal kallikrein and nitric oxide production.

The nutritional control of ghrelin secretion in humans

The nutritional control of ghrelin has not been fully clarified yet. Particularly, the influence of aminoacids and lipids is controversial and, moreover, whether the intraluminal gastric contact with nutrients is required or if the modulatory action of nutrients on ghrelin secretion is mediated by insulin is still matter of debate. To clarify the role of nutrients in the control of ghrelin secretion evaluating the effects of intravenous and oral lipids and aminoacids compared with glucose and fructose load in healthy subjects. A total of 6 healthy overnight-fasted volunteers underwent the following testing sessions: (a) iv arginine (ARG, 0.5 g/kg); (b) oral protein load (PRO, 50 g); (c) iv lipid-heparin infusion (Li He, Intralipid 10% 250 ml); (d) oral fat load (OIL, soy oil 40 g); (e) oral glucose load (OGL, 100 g); (f) oral fructose load (OFL, 100 g); (g) iv saline (SAL, 3 ml); (h) oral water load (WL, 200 ml). Total ghrelin, insulin, and glucose were assayed every 15 min from 0 up to +180 min. WL and SAL did not modify insulin, glucose and ghrelin. ARG induced a prompt but transient increase (P < 0.05) of insulin and glucose (P < 0.01), without modifying ghrelin secretion. PRO induced a mild but sustained increase of insulin secretion (P < 0.05) without affecting glucose and ghrelin. Li-He progressively increased circulating glucose (P < 0.01) without modifying insulin and ghrelin secretion. No significant variations in circulating glucose, insulin, and ghrelin occurred after OIL. OGL significantly (P < 0.01) increased insulin and glucose levels and progressively decreased (P < 0.05) ghrelin levels. OFL induced a mild (P < 0.05) increase of insulin without modifying glucose levels. Similarly, OFL was followed by a milder decrease (P < 0.05) of ghrelin levels. Differently from carbohydrates and independently from their modulatory effect on insulin secretion and glucose levels, both lipids and aminoacids play a negligible role in the acute control of ghrelin secretion either after acute enteral and parenteral administration.

Protein-sensitive hypoglycemia without leucine sensitivity in hyperinsulinism caused by K ATP channel mutations

Because children with congenital hyperinsulinism (HI) caused by recessive loss of function mutations in the adenosine triphosphate (ATP)-dependent potassium channel (K(ATP)-HI) are not leucine sensitive, we evaluated for protein-induced hypoglycemia with oral protein tolerance tests. Blood glucose and insulin concentrations were measured every 15 minutes for 3 hours after an oral protein load in children with K(ATP)-HI (n = 11) and compared with those of children with glutamate dehydrogenase HI (n = 12) and control subjects (n = 12). Similar to children with glutamate dehydrogenase HI, patients with K(ATP)-HI displayed protein-induced hypoglycemia (10/11) with blood glucose concentrations declining by 17 to 69 mg/dL. In contrast, oral protein had little effect on blood glucose concentrations in control subjects. Protein-induced hypoglycemia is a feature of K(ATP)-HI, despite the absence of leucine sensitivity. The results indicate that amino acids can stimulate insulin secretion via a glutamate dehydrogenase- and K(ATP) channel-independent pathway.