Circulating somatostatin acts on the islets of Langerhans by way of a somatostatin-poor compartment.

Somatostatin perfused in canine pancreases at 10 to 20 picograms per milliliter or 10 to 20 percent of the pancreatic vein somatostatin concentration inhibited insulin and glucagon secretion. This suggests that the high local concentration of endogenous somatostatin is not in contact with somatostatin receptors of the islets. The integrity of this separation may determine the sensitivity of islet cells to circulating somatostatin.

Properties of endogenous somatostatin-like immunoreactivity and synthetic somatostatin in dog plasma.

Somatostatin-like immunoreactivity (SLI) in the peripheral venous plasma of dogs and in their pancreatic and gastric venous effluents was characterized and compared with synthetic somatostatin. Both endogenuous plasma SLI and somatostatin added to plasma were eluted from Sephadex gels at pH 8.8 in the 150,000--200,000-mol wt region but at pH 2.5 both appeared in the 1,500--2,000-mol wt region. The SLI released from the isolated dog pancreas perfused with plasma-free buffer was eluted entirely as a 1,600-dalton polypeptide, but when the pancreas was perfused with plasma, SLI was eluted in the 150,000--200,000-mol wt zone. Affinity chromatography of plasma samples on immobilized antibodies directed against the central portion of the somatostatin molecule (residues 5--9 and 11) removed approximately equal to 90% of both endogenous SLI and somatostatin added to plasma, but neither was removed by affinity chromatography on antibodies directed against the NH2-terminal region of somatostatin (residues 1--4). The SLI from plasma and from pancreas perfusate isolated by affinity chromatography was identical in molecular size, charge, and immunometric properties to synthetic somatostatin. It is concluded that endogenous SLI is secreted by the pancreas and stomach in a form not distinguishable from synthetic somatostatin, but circulates in plasma bound to large molecular weight components; the NH2-terminal residues of somatostatin appear to be important in this binding.

The effects of gastrin, gastric inhibitory polypeptide, secretin, and the octapeptide of cholecystokinin upon immunoreactive somatostatin release by the perfused canine pancreas.

The effects of gastrin, gastric inhibitory polypeptide, secretin, and the octapeptide of pancreozymin-cholecystokinin on immunoreactive somatostatin release were studied in the isolated perfused dog pancreas. Gastrin at a concentration of 65 ng/ml and the octapeptide of pancreozymin-cholecystokinin at a concentration of 25 ng/ml produced a prompt, but transient statistically significant, twofold rise in mean somatostatin concentration. Secretion at a concentration of 0.3 U/ml and gastric inhibitory polypeptide concentration of 58 ng/ml produced a prompt two- to threefold rise in mean somatostatin release, which persisted throughout the perfusion period. With all four polypeptides the pattern of the somatostatin response resembled that of insulin. It appears that pancreatic somatostatin release is stimulated by gastrointestinal hormones that influence the secretion of insulin and glucagon.

Release of immunoreactive somatostatin from the pancreas in response to glucose, amino acids, pancreozymin-cholecystokinin, and tolbutamide.

The effects of glucose, amino acids, pancreozymin-cholecystokinin, and tolbutamide upon the release of immunoreactive somatostatin (IRS) from the isolated perfused pancreas were studied. In seven experiments in which glucose was perfused either at a concentration of 100 or 350 mg/dl or at 25 mg/dl, IRS levels were significantly greater at the higher glucose concentrations. In three dose-response experiments in which the perfusing glucose concentration was increased at 30-min intervals from an initial concentration of 25 mg/dl to a final concentration of 300 mg/dl, progressive increases in IRS release were noted at glucose concentrations of 100 mg/dl and above. Perfusion of a 20 mM mixture of 10 amino acids also elicited a prompt and significant biphasic IRS rise in each of six experiments. In five experiments, 20 mM leucine evoked a similar response in mean IRS. Perfusion with 0.075 Ivy U/ml of pancreozymin-cholecystokinin, with or without the presence of a 1 mM 10-amino acid mixture, elicited a prompt rise in IRS with a pattern resembling that of insulin in a total of six experiments. Tolbutamide (0.75 mg/min) also stimulated IRS release in five of six challenges. The IRS responses to nutrients and to pancreozymin and their similarity to the insulin responses raise the possibility that, like insulin, pancreatic somatostatin may have an endocrine role related to nutrient homeostasis.

Fluidity difference of membrane lipids in human normal and leukemic lymphocytes as controlled by serum components.

Lymphocytes isolated from the peripheral blood of patients with chronic lymphatic leukemia and from normal healthy donors were analyzed for fluidity of membrane lipids. The degree of lipid fluidity in normal and leukemic lymphocytes was quantitatively monitored by a method based on fluorescence polarization analysis of a fluorescent probe that is embedded in lipid regions of cellular membrances. The present studies were performed on lymphocytes isolated from 26 blood samples from 16 patients with chronic lymphatic leukemia and 36 blood samples from 36 normal health donors. A signifcant increase in the degree of fluidity of membrane lipids was found in lymphocytes isolated from leukemic patients as compared to that found for lymphocytes isolated from healthy donors. In vitro incubation of leukemic lymphocytes in normal serum resulted in a decrease in the fluidity of cellular membranes, whereas incubation of normal lymphocytes in leukemic serum resulted in an increase in the fluidity of membrane lipids. These observations suggest that normal and leukemic lymphocytes can be quantitatively characterized by monitoring degree of fluidity of cellular membrane lipids and that the fluidity difference between normal and leukemic lymphocytes is controlled by components in the blood serum.

Pulsatile insulin secretion in isolated rat islets.

The pancreas secretes insulin in an oscillatory fashion, but the precise site of the pacemaker for pulsatile insulin secretion has not been identified. These studies were designed to determine whether islets also secrete insulin in a pulsatile fashion if they are isolated from their pancreatic milieu. Isolated rat islets (80-100) were perifused 8 h in culture medium after overnight incubation, and samples were collected at 3.3-min intervals. Insulin secretion was evaluated for pulsatility with the Clifton Cycle Detection Program. Perifusion of islets was associated with a spontaneous, persistent, and regular pulsatility of insulin secretion, which was observed in all conditions tested. Perifusion with medium containing 5.5 mM glucose (n = 11) demonstrated oscillations with a mean periodicity of 17.6 +/- 1.1 min and a mean amplitude of 4.8 +/- 0.4 microU/ml when overall mean insulin concentration was 16.7 +/- 2.4 microU/ml. When the glucose concentration was 16.7 mM (n = 9), overall mean insulin concentration was 54.4 +/- 2.6 microU/ml, with increases in periodicity (22.0 +/- 1.3 min) and amplitude (10.7 +/- 0.5 microU/ml). All measurements were significantly different from those observed during perifusion with 5.5 mM glucose (P less than 0.02-0.001). Theophylline (1 mM) also enhanced the overall mean insulin concentration and amplitude (69.4 +/- 10.4 and 14.2 +/- 1.2 microU/ml, respectively) compared with control studies without theophylline (16.7 +/- 5.3 and 4.3 +/- 0.5 microU/ml) (P less than 0.01). The period of the cycle was also increased from 17.5 +/- 1.1 to 26.4 +/- 6.3 min, but this was not significantly different from the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Somatostatin impairs clearance of exogenous insulin in humans.

Somatostatin has been widely used to suppress endogenous pancreatic hormone secretion in research studies. Many of these studies required the simultaneous infusion of a hormone together with somatostatin. A critical assumption for its use in metabolic investigation is that somatostatin has no effect on the action or clearance of a concomitantly infused hormone. To test whether clearance of an exogenously infused hormone is affected, we infused insulin with or without somatostatin in two sets of studies. Insulin (40 mU X kg-1 X h-1) was infused for 100 min (n = 6). Plasma glucose levels fell to 55 +/- 4.1 mg/dl with insulin alone and significantly lower, to 44 +/- 1.9 mg/dl, when somatostatin (250 micrograms/h) was also infused (P less than .01). Plasma immunoreactive insulin (IRI) rose to 57 +/- 12.5 microU/ml with insulin alone, which was significantly different from 88 +/- 15 microU/ml when insulin was infused together with somatostatin (P less than .01). When a smaller dose of insulin (30 mU X kg-1 X h-1) was infused for 100 min (n = 4), similar results were observed. When somatostatin was infused together with insulin, plasma glucose fell to lower levels (41 +/- 4.2 vs. 62 +/- 9.5 mg/dl; P less than .01) and plasma IRI rose higher (39 +/- 8.5 vs. 27 +/- 5.9 microU/ml; P less than .01) than when insulin was infused alone. C-peptide was equally suppressed by hypoglycemia regardless of whether somatostatin was administered, indicating suppression of endogenous insulin during these studies. We conclude that somatostatin infusion impairs the clearance of exogenous insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

Glucose entrainment of high-frequency plasma insulin oscillations in control and type 2 diabetic subjects.

Regular high-frequency oscillations of insulin secretion are characteristic of normal beta-cell function. These oscillations are easily entrainable to an exogenous rhythm by small changes in glucose concentration in vitro. We tested whether high-frequency insulin oscillations in vivo would also be entrainable by glucose and whether a lack of entrainment would characterize the diabetic beta-cell. We tested 13 control subjects and 11 patients with type 2 diabetes. Subjects underwent serial blood sampling at 1-min intervals for 60-120 min in the basal state or with small (15 mg/kg) boluses of glucose injected intravenously at exact 29-min intervals. Time series analysis was carried out using spectral analysis. Oscillations of basal plasma glucose concentrations were observed in both control and type 2 diabetic subjects, with a mean period of 11.3 +/- 3.1 and 11.6 +/- 2.0 min, respectively. These oscillations were entrained to mean periods of 15.0 +/- 0.6 and 14.2 +/- 0.9 min, respectively, by exogenous glucose. Regular high-frequency insulin oscillations were observed in control subjects; the mean period of basal plasma insulin oscillations was 10.7 +/- 1.2 min and was entrained to exogenously injected glucose, with a period of 15.2 +/- 0.1 min. In contrast, in the type 2 diabetic subjects, spontaneous insulin oscillations were unchanged by the glucose rhythm; the mean periods were 10.0 +/- 1.0 min during the basal period, and 10.1 +/- 0.0 min during glucose injections. These results demonstrate that spontaneous high-frequency insulin oscillations can be successfully entrained by glucose in control subjects. However, these oscillations in type 2 diabetic subjects are not similarly entrained. We conclude that loss of entrainment of spontaneous high-frequency insulin oscillations in type 2 diabetes is a highly sensitive manifestation of beta-cell secretory dysfunction.

Naloxone decreases centrally induced hyperglycemia in dogs. Evidence for an opioid role in glucose homeostasis.

Intracerebroventricular (ICV) instillation of morphine and beta-endorphin causes centrally induced hyperglycemia. Locally active, endogenous opioids in the central nervous system may, therefore, also be involved in the elevation of blood sugar. This possibility was tested by examining the glucoregulatory response to central glucoprivation induced by ICV administration of 2-deoxy-D-glucose (2DG) in dogs. Administration of 2DG resulted in a rise in plasma glucose and immunoreactive glucagon (IRG) of 108 +/- 19 mg/dl and 70 +/- 20 pg/ml, respectively. These changes were attenuated by the simultaneous central infusion of the opiate antagonist naloxone: plasma glucose levels increased by 77 +/- 14 mg/dl and IRG by 43 +/- 3 pg/ml, both significantly different from the effect of 2DG alone (P less than 0.05-0.01). These findings suggest that opiate receptors participate in the counterregulatory response to central glucoprivation. They also provide a mechanism by which endogenous opioid peptides may play a role in the central regulation of glucose homeostasis.

Sustained pulsatile insulin secretion from adenomatous human beta-cells. Synchronous cycling of insulin, C-peptide, and proinsulin.

The endocrine pancreas secretes insulin in a pulsatile fashion. This rhythm is generated at a site within the pancreas, although its precise location has not been determined. With an in vitro system, we tested the possibility that beta-cells might generate spontaneous pulsatile insulin secretion in the absence of any external influence. Human insulinoma tissue from five patients was perifused for 7-10 h with RPMI-1640 medium and constant concentrations of glucose (5.5 mM). Insulin, C-peptide, and proinsulin were measured in the effluent collected at 3.3-min intervals. All three peptides demonstrated pulsatility of secretion in a similar, synchronous fashion that was sustained throughout each study. The Clifton cycle detection program demonstrated cycling in all five tumors, with an average period for all tumors of 28, 29, and 26 min for insulin, C-peptide, and proinsulin, respectively. Spectral analysis confirmed the regularity and consistency of the hormonal secretory patterns. Mean hormone concentrations secreted by different tumors varied, but insulin and C-peptide were secreted in a nearly 1:1 ratio. This study demonstrates 1) that beta-cells are able to generate spontaneous pulsatile insulin secretory activity, which is independent of innervation or the presence of other islet cells, and 2) proinsulin secretion from the beta-cell also has an inherent pulsatility. The synchrony observed in the cycles of proinsulin and its peptide products confirms their common secretory pathway in the beta-cell. We conclude that the beta-cell may be the originator of insulin cycling.

Accuracy of plasma glucose measurements in the hypoglycemic range.

OBJECTIVE: This study was designed to evaluate three different enzymatic methods for glucose measurement in plasma samples with special emphasis on glucose concentrations in the hypoglycemic range. RESEARCH DESIGN AND METHODS: Glucose dehydrogenase (Hemo-Cue analyzer), glucose oxidase (YSI analyzer), and hexokinase (Abbott analyzer) methods were used to measure plasma samples that were obtained during research studies. RESULTS: Mean glucose concentrations (n = 240) were 5.3 +/- 0.2, 5.4 +/- 0.2, and 5.6 +/- 0.2 mM (95.6 +/- 3.9, 96.7 +/- 3.9, and 101.6 +/- 4.0 mg/dl) using glucose dehydrogenase, glucose oxidase, and hexokinase, respectively (NS). In the hypoglycemic range, mean glucose concentrations with each method retained the same hierarchy of measurements: 2.7 +/- 0.05, 2.8 +/- 0.04, and 2.9 +/- 0.03 mM (48.4 +/- 0.9, 50.6 +/- 0.8, and 52.3 +/- 0.6 mg/dl) by glucose dehydrogenase, glucose oxidase, and hexokinase, respectively (P < 0.005). Individual glucose dehydrogenase measurements (n = 240) correlated well with glucose oxidase and hexokinase, r = 0.99, and were considerably easier to perform at the bedside. The differences between the glucose measurement methods were consistent and similar in low, normal, and high concentration ranges. CONCLUSIONS: We conclude that any interpretation or comparison of critical clinical and research measurements of glucose in different settings take into account methodological differences, particularly in the hypoglycemic range.

Morphine-induced hyperglycemia: role of insulin and glucagon.

An iv bolus injection of 0.5 mg/kg morphine, about twice the therapeutic dose, caused plasma glucose to rise more than 120 mg/dl in alloxan-diabetic conscious dogs but had little effect on conscious normal dogs. Plasma glucagon rose in the diabetic and nondiabetic groups by 30 +/- 10 and 100 +/- 29 pg/ml, respectively, but insulin levels increased significantly only in the nondiabetics. The hyperglycemic action on morphine may, at least in part, be the result of an increase in glucagon secretion without a sufficient accompanying release of insulin.

Somatostatin analogs inhibit somatostatin release.

To determine if, like insulin, somatostatin inhibits its own secretion from the pancreas, nonimmunoreactive analogs of somatostatin were perfused in an isolated dog pancreaticoduodenal preparation using a nonrecirculating system. [D-Trp8-D-Cys14]somatostatin, at a concentration of 200 ng/ml, blocked the response of somatostatin-like immunoreactivity (SLI) to cholecystokinin and arginine. When perfusion of the analog was discontinued, SLI release increased. At a concentration of 0.1 ng/ml, des Asn5-[D-Trp8]somatostatin lowered SLI levels significantly without significantly reducing glucagon levels. At a concentration of 1 ng/ml, des Asn5-[D-Trp8]somatostatin significantly inhibited SLI as well as insulin and glucagon release. Perfusion of glucagon at a concentration of 10 ng/ml failed to overcome the blockade of SLI and insulin release caused by 50 ng/ml des Asn5-[D-Trp8]somatostatin. The results are compatible with a direct inhibitory effect of somatostatin analogs upon SLI release and raise the possibility of a self-inhibiting action of the native hormone.

Sparing of cognitive function in mild hypoglycemia: dissociation from the neuroendocrine response.

Central nervous system function during insulin-induced reductions in plasma glucose was studied by measuring plasma epinephrine concentrations and testing cognitive function. Mild glucose reduction [mean plasma glucose, 62 +/- 3 (+/- SEM) mg/dL (3.4 +/- 0.2 mmol/L)] was induced with an iv insulin infusion at the rate of 40 mU/kg.h for 180 min in 7 normal subjects. Despite a marked increase in mean plasma epinephrine concentrations, which peaked at 426 +/- 68 pm/mL (2325 +/- 371 pmol/mL; P less than 0.001), no significant differences in cognitive function occurred as determined by a series of trail-making tests compared with the results of serial tests in a group of 17 control subjects. In contrast, when hypoglycemia was induced (plasma glucose, less than 42 mg/dL; 2.3 mmol/L) by bolus injection of insulin in 4 normal subjects, cognitive function was impaired in every subject, as demonstrated by a delay in completion of the trail-making test. The mean completion time was prolonged to 107 +/- 16% of the baseline at the time of hypoglycemia vs. 74 +/- 4% in control subjects (P less than 0.01). These findings suggest that cognitive function may be spared during mild plasma glucose reductions and is dissociated from the neuroendocrine adrenergic response that is activated under these conditions. This dissociation may be part of a homeostatic process in which overall brain function is maintained during glucoprivation, although counterregulation has already been triggered to prevent a further decrease in plasma glucose.

Acute effects of high fat and high glucose meals on the growth hormone response to exercise.

The health promoting, anabolic effects of physical activity may be mediated, in part, by an exercise-associated increase in GH. However, little is known about the acute effects of diet on exercise-induced GH release. We hypothesized that a single meal could attenuate the GH response to exercise by modulating substances like somatostatin, insulin, or glucose. Eleven healthy young adults performed 10 min of high intensity, standardized cycle ergometry in the morning following an overnight fast. On separate days they ingested a noncaloric placebo liquid meal or an isovolemic, isocaloric liquid meal high in either fat or glucose. Venous blood samples were obtained before and for 90 min after exercise began, whereas gas exchange data were measured breath by breath. Peak mean oxygen consumption (VO2) was, on average, 9-fold greater than preexercise levels in all groups. Although there was no difference in preexercise GH levels, mean peak, postexercise GH was 54% lower after the high-fat meal compared with placebo (P < 0.01). Modest decreases in GH response to exercise after the high-glucose meal were not statistically significant. Mean serum somatostatin was significantly higher after the high-fat meal compared with both high glucose and placebo meals. This study demonstrates that exercise-induced GH release can be significantly attenuated by the contents of a single preexercise meal. The high fat meal increased circulating somatostatin and was associated with an inhibition of the GH secretion. The data provide a possible specific mechanism to explain how diet can acutely modulate the anabolic effects of exercise.

An overnight insulin infusion algorithm provides morning normoglycemia and can be used to predict insulin requirements in noninsulin-dependent diabetes mellitus.

Initial insulin requirements in noninsulin-dependent diabetes mellitus (NIDDM) are difficult to estimate because of individual variability in insulin sensitivity and secretion. We evaluated a simple, nurse-managed algorithm for overnight delivery of insulin, for its ability to provide morning near-normoglycemia and as a means to predict initial insulin requirements in NIDDM. Twenty-seven patients with poorly controlled NIDDM were studied on 30 occasions. A 12-h iv insulin infusion was begun at 2000 h, and bedside blood glucose concentrations were measured at hourly intervals. The rate of insulin infusion was adjusted according to blood glucose levels. We estimated the preprandial insulin dose requirement for the following day in 16 patients based on overnight insulin requirements to maintain normoglycemia. Preprandial insulin doses were adjusted for prevailing blood glucose concentrations. At 2000 h, the mean (+/-SEM) blood glucose concentration was 265.7 +/- 10.8; at 0300 h, it was 122.8 +/- 3.4; and at 0700 h, it was 123.8 +/- 5.1 mg/dL. On the next day, mean blood glucose levels (before and 2 h after a meal) were: breakfast, 102.5 +/- 5.9 and 177.3 +/- 19.2; lunch, 138.9 +/- 15.5 and 136.3 +/- 11.4; dinner, 105.7 +/- 7.2 and 178.1 +/- 15.7 mg/dL. There was no significant difference between mean calculated and administered total insulin dosage the next day (84.2 +/- 7.0 vs. 78.2 +/- 8.2 U). Thus, a weight-based algorithm for iv insulin infusion induced near-normoglycemia in NIDDM and successfully predicted the insulin dose requirement. We conclude that initiating insulin therapy in NIDDM patients can be achieved rapidly and efficiently based on a nurse-managed overnight insulin infusion.

Erratic oscillatory characteristics of plasma insulin concentrations in patients with insulinoma: mechanism for unpredictable hypoglycemia.

Patients with insulin-producing tumors may have hypoglycemic symptoms at unpredictable times. This study evaluated whether plasma insulin oscillations, known to occur in normal individuals but not explored in patients with insulinomas, could be an underlying mechanism for such events. Nine normal subjects and five patients with proven insulinomas were studied in the fasting state. Serial sampling of arterialized blood over 80-100 min, at 2- or 3-min intervals was performed. In normal subjects, mean plasma glucose and insulin concentrations were 5.3 +/- 0.1 mmol/L and 58 +/- 9 pmol/L, respectively. Regular, low-amplitude plasma insulin oscillations were observed, with a period of 10-17 min. The subjects with insulinomas had lower mean plasma glucose and higher insulin concentrations than controls, 3.6 +/- 0.3 mmol/L (P = 0.01) and 150 +/- 42 pmol/L (P = 0.01), respectively. They also had insulin oscillations that appeared unstable as a result of variability in duration and amplitude compared with controls. The insulin pulses were irregular, and interpeak intervals varied between 4-54 min in different subjects; in some subjects, the amplitude was also variable, with sudden spontaneous pulses as high as 565 pmol/L, with an associated glucose decrement. We conclude that large spontaneous bursts of insulin secretion occur in patients with insulinomas as part of an erratic pattern of oscillatory insulin secretion, and these can account for unpredictable occurrences of hypoglycemia.

A glucose reduction challenge in the differential diagnosis of fasting hypoglycemia: a two-center study.

Investigation of patients with suspected or proven hypoglycemia is often a time-consuming and expensive process. We describe a glucose reduction challenge test which may be useful as an out-patient screening procedure. Insulin is infused for 3 h at 40 mU/kg.h. Plasma glucose was monitored at the bedside during the test, and blood samples were collected for measurement of C-peptide. Responses were examined in 17 normal controls, and 6 patients with insulinomas. In normal subjects, mean plasma glucose fell to a plateau value of 3.2 +/- 0.2 mmol/L (57 +/- 2.6 mg/dL) and remained at that level with few symptoms. In contrast, five of six patients with insulinomas developed severe hypoglycemia, with plasma glucose levels between 1.9 (34 mg/dL) and 2.2 mmol/L (39 mg/dL). Plasma C-peptide concentrations were suppressed to 0.08 pmol/mL or less in normal subjects, but in insulinoma patients remained at 0.32-1.6 pmol/mL i.e. outside the normal range, and diagnostic of nonsuppressible insulin secretion. These data demonstrate that moderate reduction of serum glucose maintained for a prolonged period results in marked suppression of plasma C-peptide, permitting improved discrimination between normal subjects and patients with insulinomas. This glucose reduction challenge can, therefore, be used as a test of glucose-regulating ability, where failure (hypoglycemia) per se represents a measurable abnormality. C-Peptide measurements will determine whether the cause of hypoglycemia is due to hyperinsulinemia.

Very-low-energy diets alter the counterregulatory response to falling plasma glucose concentrations.

A consequence of short-term very-low-energy diets (VLEDs) in lean subjects is reactive hypoglycemia. We therefore tested the responses of overweight women on prolonged (14 d) VLEDs. Subjects lost 4.8 +/- 0.2 kg (mean +/- SEM, n = 13, P < 0.001). Group A (n = 6) was challenged with an oral-glucose-tolerance test (OGTT) and group B (n = 7) with an oral-sucrose-tolerance test (OSTT) on days 1 and 14. In group A, mean nadir plasma glucose after the OGTT was lower on day 14, 3.75 +/- 0.16 vs 4.7 +/- 0.19 mmol/L (P < 0.01), because of an accelerated rate of glucose decline (RGD, 26.7 +/- 3.3 vs 17.2 +/- 3.9 mumol.l-1.min-1, P < 0.05) late in the OGTT. Plasma insulin was also lower (P < 0.03) and the VLED suppressed two growth hormone (GH) peaks on day 14 (P < 0.05 for each). In group B on day 14, a greater RGD was also observed late in the OSTT, 16.9 +/- 4.1 vs 6.5 +/- 2.0 mumol.L.min-1 (P < 0.03). GH peaks were also significantly suppressed. We conclude that a VLED results in altered glucose regulation late after carbohydrate loading, characterized by an accelerated decline in plasma glucose and GH suppression. Patients on a VLED may be at risk for abnormally low plasma glucose concentrations when ingesting high carbohydrate loads.

Plasma glucose thresholds for counterregulation after an oral glucose load.

Glucose counterregulation (GCR) plays an important role in the transition between exogenous and endogenous glucose delivery after an oral glucose load. This response is initiated when plasma glucose concentrations are decreased below threshold levels, previously defined in studies of insulin-induced hypoglycemia. In this study, we tested the plasma glucose thresholds for activation of the GCR response under more physiologic circumstances, ie, after glucose ingestion. We studied 20 normal subjects for 300 minutes after 75 g of oral glucose. Between 150 and 300 minutes, blood samples and symptom scores were obtained at 10-minute intervals. After oral glucose, individual glucose nadirs were observed over a wide time range (160 to 290 minutes). Mean glucose concentrations decreased from 5.3 +/- 0.2 mmol/L at 30 minutes before the nadir (-30 minutes) to 3.8 +/- 0.2 mmol/L at the nadir (0 minutes). Mean plasma epinephrine concentrations increased from 210 +/- 35 pmol/L, were significantly elevated at -10 minutes (P < .05), and peaked at +20 minutes (1,008 +/- 184 pmol/L, P < .001). Mean plasma glucagon concentrations were significantly increased over baseline (100%) at +10 minutes (P < .001) and peaked at +30 minutes (122% +/- 7%, P < .001). Seven subjects (out of 15 tested) developed symptoms. Quantitative evaluation revealed a peak in the mean symptom score at +20 minutes, an increase from 0.4 +/- 0.3 to 2.6 +/- 0.1 arbitrary units (P < .06).(ABSTRACT TRUNCATED AT 250 WORDS)