Abstract. Dietary carbohydrate accentuation of endogenous triglyceride production has been studied in 33 patients. A broad and relatively continuous spectrum of steady-state plasma triglyceride concentrations was produced in 31 of the 33 subjects during 3 wk of a high carbohydrate (fat-free) liquid formula diet. Two patients developed plasma triglyceride concentrations in excess of 2000 mg/100 ml, and these were the only patients we have studied in which carbohydrate induction of hypertriglyceridemia seemed to be associated with a defect in endogenous plasma triglyceride removal mechanisms. In the remaining 31 patients the degree of hypertriglyceridemia was highly correlated with the insulin response elicited by the ingestion of the high carbohydrate formula (P < 0.005). No significant correlation existed between fasting plasma triglyceride concentration and either plasma glucose or free fatty acid concentrations after the high carbohydrate diet, nor was the degree of hypertriglyceridemia related to degree of obesity. It is suggested that hypertriglyceridemia in most subjects results from an increase in hepatic triglyceride secretion rate secondary to plasma insulin concentration.

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In order to evaluate the relation between insulin responses, glucose loads and glucose disappearance rate, normal subjects were given glucose doses from 0.5 to 40 g by rapid intravenous injection. A highly linear correlation was seen between dose and the rapidly attained peak plasma glucose level measured as either the mean of the 3-through 5-min (3-5') absolute (r=+.98) or 3-5' incremental (A) (r=+.98) glucose value, suggesting any of these parameters can be employed as an index of the glucose stimulus. Estimated from the 3-5' A plasma insulin levels, the early insulin response, which has been previously shown to be derived from a functional pool of stored insulin, increased in a nonlinear manner over the entire dosage range. In contrast, the total incremental insulin area increased linearly (r = +.85) with increasing glucose loads, suggesting that the total insulin output proportionally responds to the size of the glucose dose. Glucose tolerance measured as the glucose disappearance rate (KG) was also a nonlinear function of glucose dose and therefore was highly correlated (r = +.72) with the acute insulin response but less well with the total incremental insulin output. Furthermore, within the 20 g glucose dose, the KG was highly correlated with the acute insulin response (r= +.66) but not with total insulin output (r= +.04). These observations suggest that the storage pool of readily available insulin is small and finite and the magnitude of the response from this pool is an important determinant of intravenous glucose tolerance (KG). (J Clin Endocr 33: 409, 1971)

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Fasting plasma glucose levels and glycosuria were measured in untreated diabetic subjects on basal and on fat free, high carbohydrate diets. On the high carbohydrate diet the mean fasting plasma glucose was slightly, but not significantly, increased by 15 mg./100 ml. and the twenty-four hour excretion of glucose was increased by 56 gm./24 hr. (p &lt; .02). Five of these subjects were restudied following insulin or oral sulfonylurea therapy, and four similar patients were studied only while on this therapy. In these treated diabetic subjects receiving the high carbohydrate diet, fasting plasma glucose was significantly decreased by 22 mg./100 ml. plasma (p &lt; . 0 2); glycosuria did not change. Thus, among diabetics, only those who remain untreated have worsened glucose tolerance on fat free, high carbohydrate diets.

A B S T R A C T An epinephrine infusion of 6 gsg/min decreased the rapid insulin response to a 5 g glucose pulse by 96% (P < 0.001) compared with the preinfusion control. In contrast when an identical epinephrine infusion was superimposed on a prolonged glucose infusion, elevated steady-state insulin levels did not decrease, but increased from 26.9 ±6 (mean -+SD, UU/ml) to 56.8 ±15 AU/ml (P < 0.05) in parallel with the epinephrineinduced hyperglycemia. Thus epinephrine inhibition of insulin secretion was observed during acute but not chronic glucose stimulation. To evaluate further the insulin responses during a prolonged glucose infusion, a 5 g glucose pulse was given iefore and 60 min later during a concomitant epinephrine infusion. Although the acute insulin response to the first glucose pulse was observed during the elevated steady-state glucose and insulin levels associated with the glucose infusion, epinephrine again inhibited the acute insulin response to the subsequent 5 g glucose pulse by 91% (P < 0.01 ). Thus epinephrine appears to inhibit selectively the rapid insulin response to glucose but not to influence insulin output stimulated by prolonged hyperglycemia. These observations provide further evidence for a model of insulin secretion which includes a small storage pool available for immediate release to a glucose challenge and a more slowly responding pool regulating insulin secretion in the basal and steady state.

A B S T R A C T Secretin-stimulated insulin release was studied in normal subjects. In response to rapid intravenous injections (pulses) of secretin, insulin levels reached a peak between 2 and 5 min and returned to basal levels with 15 min. In contrast to large glucose pulses, increasing secretin pulses did not elicit sustained or prolonged insulin responses. In addition, insulin responses to a pulse and infusion were essentially identical with that of a pulse alone. Increasing secretin pulses given in 1 day were associated with decreasing insulin responses but not when the same pulses of secretin were given over a 2 day period. When time was the sole variable, insulin responses progressively decreased after identical 15-U secretin pulses given every 30 min, but were unchanged when the interval was 105 min. These observations indicate that secretin in contrast to glucose stimulates insulin release which is uniphasic. They suggest that release occurs only from a stored, readily available pool. This insulin pool appears to be relatively small and can be discharged faster than it refills.

A B S T R A C T To investigate a possible action of insulin on the glomerulus, the binding 1251-insulin to the isolated glomeruli prepared from rat kidney was examined. When incubated at 22°C, '251-insulin binding proceeded with time and reached a steady state at 45 min at which time nonspecific binding was <25% of total binding. A small fraction of '25I-insulin was degraded during incubation. This binding was specific to insulin in that it was inhibited by unlabeled porcine and beef insulins and to a lesser extent by porcine proinsulin and desalanine-desasparagine insulin, but not by glucagon, parathyroid hormone, vasopressin, calcitonin, and angiotensin II. Increasing concentrations of nonlabeled insulin displaced 1251-insulin binding in a dose-dependent fashion. Scatchard plot of the data was curvilinear consistent with either two classes of receptors with different affinities or a single class of receptors that demonstrate negative cooperativity. The addition of excess nonlabeled insulin to the glomeruli preincubated with 1251-insulin resulted in a rapid dissociation of -70% of bound I251-insulin. Insulin decreased the increments in glomerular cyclic AMP levels by epinephrine and by prostaglandin E2, but not those by histamine. These data showed the presence of specific insulin receptors in the glomeruli, and that insulin action may be, at least in part, through modulation of glomerular cyclic AMP concentrations. Such action of insulin may underlie the alteration in glo-