Diffusion of Glucose, Insulin, Inulin, and Evans Blue Protein into Thoracic Duct Lymph of Man*

Rasio, E; Hampers, Constantine L.; Soeldner, J S; Cahill, George F.

doi:10.1172/jci105596

Cited by 67 publications

(43 citation statements)

References 14 publications

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“…Drainage of the thoracic duct has previously been applied to reduce the number of circulating lymphocytes in order to induce systemic immunomodulation in autoimmune disorders and after organ transplantation; the amount of lymph collected per day was in the range of 1.5 to 2 L. When patients were examined after a meal or during a secretin test, the levels of the exocrine enzymes in the lymph rose prior to and to higher concentrations than those simultaneously measured in the blood, supporting the notion of a substantial direct delivery of these enzymes into the lymph capillaries adjacent to the acini (20,21). In line with the morphological observations reported here, corresponding measurements of insulin during an intravenous glucose tolerance test gave no support for a direct delivery of insulin into lymphatic capillaries (22).…”

Section: Discussionsupporting

confidence: 48%

An Apparent Deficiency of Lymphatic Capillaries in the Islets of Langerhans in the Human Pancreas

Korsgren

2016

Diabetes

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The lymphatic system is crucial for efficient immune surveillance and for the maintenance of a physiological pressure in the interstitial space. Even so, almost no information is available concerning the lymph drainage of the islets of Langerhans in the human pancreas. Immunohistochemical staining allowed us to distinguish lymphatic capillaries from blood capillaries. Almost no lymphatic capillaries were found within the islets in pancreatic biopsy specimens from subjects without diabetes or from subjects with type 1 or type 2 diabetes. Lymphatic capillaries were, however, found at the islet-exocrine interface, frequently located along blood capillaries and other fibrotic structures within or close to the islet capsule. Lymphatic capillaries were regularly found in the exocrine pancreas, with small lymphatic vessels located close to and around acini. Larger collecting lymphatic vessels were located in fibrotic septa between the exocrine lobules and adjacent to the ductal system of the pancreas. In summary, we report a pronounced deficiency of lymphatic capillaries in human islets, a finding with implications for immune surveillance and the regulation of interstitial fluid transport in the endocrine pancreas as well as for the pathophysiology of both type 1 and type 2 diabetes.

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Section: Discussionsupporting

confidence: 48%

An Apparent Deficiency of Lymphatic Capillaries in the Islets of Langerhans in the Human Pancreas

Korsgren

2016

Diabetes

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“…After three basal samples from Ϫ150 to Ϫ120 min, a continuous infusion of somatostatin (1.0 g ⅐ min Ϫ1 ⅐ kg Ϫ1 ; Bachem, Torrance, CA) was begun to suppress endogenous insulin secretion, and porcine insulin was infused into the femoral vein and maintained from Ϫ120 to 180 min for a total period of 5 h. During this insulin infusion, glucose was measured in 10-min intervals during the first 60 min and in 15-min intervals thereafter, and plasma glucose was clamped to basal levels by variable infusion of 50% glucose labeled with [3-3 H]-D-glucose (2.7 Ci/g glucose). Also, at 0 min, an intravenous bolus of [ 14 C]inulin (0.8 Ci/kg body wt) was given into a saphenous vein, and rapid samples for the measurement of the kinetic profile of [ 14 C]inulin were collected at 1, 2, 3, 4, 5,6,8,10,12,15,17,20,25,30,35,40,45,50, and 60 min and in 15-min intervals until the end of the experiment at 180 min. Protocol 2 (anesthetized study, sequential approach with interstitial fluid access).…”

Section: Methodsmentioning

confidence: 99%

“…The faster equilibrating compartment is assumed to be supplied by capillaries in the splanchnic bed that are porous and lack a continuous investment of the basement membrane, whereas skeletal muscle is assumed to account for a major component of the slowly equilibrating interstitial fluid compartment. Parameter k 01 represents the irreversible clearance of inulin from the plasma compartment by the kidney (18,20), and transport between plasma and slow (k 21 , k 12 ) and rapid (k 31 , k 13 ) equilibrating compartments was assumed to occur by passive diffusion (…”

Section: Pharmacokinetic Data Analysis: [mentioning

confidence: 99%

“…Before insulin can reach the target cells in skeletal muscle and adipose tissue to stimulate glucose disposal, it has to traverse the tight capillary endothelium between plasma and interstitial fluid that bathes cells (11,12), and it has been demonstrated that this transport mechanism is ratelimiting for the stimulation of glucose uptake (13,14). Therefore, it could be important if insulin would exploit its microvascular action not only to stimulate tissue recruitment for small metabolites but also to act as a stimulus for its own distribution to the cell.…”

mentioning

confidence: 99%

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Physiological Hyperinsulinemia in Dogs Augments Access of Macromolecules to Insulin-Sensitive Tissues

et al. 2004

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The present results show that physiological hyperinsulinemia will enhance the delivery of a substance of similar molecular size to insulin to previously less intensively perfused regions of insulin-sensitive tissues. Our data suggest that the delivery of insulin itself to insulin-sensitive tissues could be a mechanism of insulin action on cellular glucose uptake independent of and possibly synergistic with either enhanced blood flow distribution or GLUT4 transporter recruitment to enhance glucose utilization. Because of the differences between inulin and insulin itself, whether delivery of the bioactive hormone is increased remains speculative.

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“…Lithell et al [32] also found increased insulin concentrations in the fasting state as well as at the end of an intravenous glucose tolerance test during b-blocking treatment, and the individual changes were inversely correlated with capillary density in skeletal muscle. The transendothelial insulin transport is an important regulator of the interstitial insulin concentration, which is normally lower than in plasma [33]. Changes in blood flow may thus affect the amount of insulin delivered to the interstitial fluid [34].…”

Section: Discussionmentioning

confidence: 99%

The effect of metoprolol treatment on insulin sensitivity and diurnal plasma hormone levels in hypertensive subjects

Guðbjörnsdóttir¹,

Fowelin²,

Elam³

et al. 1997

Eur J Clin Investigation

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Abstract.To evaluate the effect of metoprolol on insulin sensitivity and diurnal plasma hormone levels, seven mildly hypertensive subjects were investigated (four men and three women, age 52 Ϯ 8, body mass index 25 . 4 Ϯ 1 . 9, mean Ϯ SD). The study had a placebo-controlled, double-blind, crossover design with 6 weeks' metoprolol treatment (100 mg b.i.d) vs. placebo. At the end of each treatment period 24-h blood samples were collected continuously for diurnal analysis of hormone levels and a hyperinsulinaemic euglycaemic clamp combined with [3-3 H]-D-glucose infusion was performed. Insulin sensitivity was evaluated by means of three different methods: diurnal plasma insulin and glucose levels; glucose consumption; and insulin sensitivity index during euglycaemic clamp conditions. Fasting blood glucose and insulin concentrations as well as mean plasma diurnal levels of insulin, growth hormone, testosterone and cortisol were similar after placebo and metoprolol treatment, whereas noradrenaline and adrenaline levels were significantly increased after metoprolol. During the clamp, plasma insulin was significantly higher after metoprolol treatment than after placebo treatment (56 Ϯ 3 vs. 64 Ϯ 2 mU L -1 , P < 0 . 05). Consequently, the insulin sensitivity index [glucose infusion rate (GIR)/ plasma insulin] was lower after metoprolol treatment (16 . 1 Ϯ 2 . 6 vs. 10 . 2 Ϯ 1 . 2, P < 0 . 05), although GIR was not significantly changed. We suggest that the insulin sensitivity index may not accurately reflect the insulin effect as the plasma level of insulin was significantly increased during insulin infusion but not at 24 h, possibly because of alteration of distribution and/or degradation rate of exogenous insulin. Thus, the likelihood of metoprolol inducing insulin resistance in hypertensive subjects may be less than previously proposed.

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Diffusion of Glucose, Insulin, Inulin, and Evans Blue Protein into Thoracic Duct Lymph of Man*

Abstract: Summary. Immunoreactive insulin, like inulin, quickly equilibrates with interstitial fluid, as evidenced by recovery in thoracic duct lymph in man. Insulin-like activity not accounted for by immunoreactive insulin behaves as a large protein and is confined to the vascular compartment.

Cited by 67 publications

References 14 publications

An Apparent Deficiency of Lymphatic Capillaries in the Islets of Langerhans in the Human Pancreas

An Apparent Deficiency of Lymphatic Capillaries in the Islets of Langerhans in the Human Pancreas

Physiological Hyperinsulinemia in Dogs Augments Access of Macromolecules to Insulin-Sensitive Tissues

The effect of metoprolol treatment on insulin sensitivity and diurnal plasma hormone levels in hypertensive subjects

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