Phillip H. Smith

Human adipose tissue lipoprotein lipase: comparison of assay methods and expressions of activity.

Summary There was a positive correlation in normal man between heparin releasable lip-oprotein lipase and lipoprotein lipase of ammonium hydroxide homogenate of acetone-ether powder in adipose tissue. Heparin releasable as lipoprotein lipase activity was about twice as high as the enzymatic activity in acetone powder, even though 40-70% of the original activity remained in the tissue after incubation with heparin. This might indicate that activation of the enzyme is associated with its release by heparin from tissue. The lipoprotein lipase activity per unit weight and per fat cell were affected differently by obesity: In obese subjects lipoprotein lipase per unit weight was proportionally lower than the activity per fat cell. The expression of activity per fat cell appears to avoid the effect of obesity, and hence increased fat cell size, on values obtained.

Stimulation by gastric inhibitory polypeptide of insulin and glucagon secretion by rat islet cultures.

Summary Physiologic amounts of GIP stimulated the secretion of IRI and IRG by monolayer cultures of neonatal rat pancreatic islets. Localization of exogenous GIP to a minority subpopulation of the islet cells was observed. The results may be interpreted to indicate that the effect of GIP on IRI release by the B cell is not direct, but rather, is mediated through its action on another islet cell type. Conversely, the action of GIP on IRG release may be directly mediated through an effect of GIP on the A cell. The action of GIP on IRG release apparently overrides any sup pressive effect that high glucose levels may exert. The stimulation by GIP of both IRI and IRG release was greater when a mixture of amino acids was omitted.

Immunohistochemical localization of somatostatin-containing cells in the intestinal tract: A comparative study

Abstract Using the peroxidase-antiperoxidase immunocytochemical technique, intestinal tissues of the rat, Japanese quail, lizard, mudsucker, and Pacific hagfish were examined to evaluate the phylogenetic distribution of somatostatin-like immunoreactive cells. Somatostatinpositive cells were observed in the intestinal tract of the rat, quail, and lizard, whereas positive staining was not observed in the gut of the mudsucker or Pacific hagfish. Since somatostatin may play a role in digestive physiology of mammals, these results suggest that this polypeptide might also affect the intestinal function of birds and reptiles. The absence of somatostatin-containing cells in the intestinal tract of teleost and cyclostomes may indicate that this hormone does not have a role in digestive physiology of these forms.

Interaction of somatostatin with the A and B cells of the endocrine pancreas

Abstract The control of islet function involves a complex interaction between substrates, hormones, and neural regulators. The presence of somatostatin-like immunoreactivity in the D cells of the islets and the potent inhibition of insulin and glucagon secretion by synthetic somatostatin make it likely that somatostatin participates in this regulation of A and B cell function. Clarification of its potential physiological role depends on a better understanding of its mechanism of action and its interaction with other controllers of islet function. Therefore, we designed a study to (1) examine the interaction of somatostatin with the alpha-adrenergic control of A and B cells, (2) evaluate the type of inhibition produced by somatostatin, and (3) study the function of somatostatin receptors of A and B cells.

Immunocytochemical localization of insulin- and somatostatin-like material in human breast tumors

Four types of human breast lesions and C3H mouse mammary adenocarcinomas (type A) were examined for the immunocytochemical localization of cells containing hormone-like substances. Insulin- or somatostatin-like immunoreactive material was observed in scattered single cells and nests of tumor cells in seven of eight infiltrating duct carcinomas, and in the majority of tumor cells from an anaplastic carcinoma. A few somatostatin-immunoreactive cells were observed in only one of seven fibroadenomas studied. No immunoreactive cells were observed in mouse adenocarcinomas or in human breast dysplasias. These results suggest that cells with hormone-like immunoreactivity may be a common feature in two types of malignant human breast tumors.

Pattern of immunoreactive glucagon in portal, arterial and peripheral plasma before and after removal of glucagonoma

Gel fractionation of portal, arterial and peripheral plasma glucagon levels was performed before and after the successful removal of a glucagonoma. A 47 year old woman had symptoms of dermatitis, weight loss, anemia and diabetes mellitus over a 16 year period. Removal of the alpha-cell tumor corrected all of her symptoms. Gel filtration of portal, arterial and peripheral blood showed two peaks of glucagon radioimmunoassay activity, a higher molecular weight glucagon with a molecular weight of 9,000 and a 3,500 dalton glucagon. Five minutes after tumor removal, the higher molecular weight glucagon had disappeared completely from the arterial and peripheral blood but not from the portal vein.

Proportional inhibition of glucose-induced insulin release by somatostatin

To test the hypothesis that somatostatin is a proportional inhibitor of glucose-induced insulin release, we examined the effect of somatostatin on the release of insulin stimulated either by endogenous signals (basal), by glucose infusion, or by glucose injection. Somatostatin infusions (1.7 micrograms/min x 30 min) produced a decrement of basal insulin output from the right lobe of the canine pancreas that was proportional to the initial rate of basal insulin secretion (r = -0.87, p < 0.001, n = 16). Glucose infusions of 1-6 mg/kg/min produced much higher rates of insulin output; again, the decrement of insulin output produced by somatostatin correlated with the initial rate of insulin secretion (r = -0.68, p < 0.01, n = 16). Rapid intravenous injection of either 2 or 20 g of glucose produced a wide range of acute insulin responses (AIR). Somatostatin produced a decrement that was proportional to the original magnitude of the AIR (r = -0.70, p < 0.005, n = 16). Thus, the absolute amount of inhibition produced by somatostatin increases, not decreases, with the magnitude of the stimulus. These data suggest that the inhibitory effect of somatostatin cannot be overcome by increasing the size of glucose stimulus. Thus, exogenous somatostatin, and presumably endogenous somatostatin as well, will produce an inhibitory effect at any physiologic level of glucose stimulation than the beta-cell receives.

Immunochemical studies of an insulin-like material in the parotid gland of diabetic BB rats

Immunocytochemical and radioimmunoassay studies were performed on pancreatic and parotid tissues from diabetic BB and control Wistar rats. Compared with those of normoglycemic controls, the pancreata of diabetic BB rats generally lacked insulin-containing Bcells. Extracts from the parotid glands of diabetic rats contained less immunoassayable insulin-like material than was present in parotid extracts of controls. However, the parotid glands of both groups of animals contained numerous cells displaying insulin-like immunoreactivity. These insulin-immunoreactive cells, located mainly in the intercalated portion of the duct system, were comparable to those we reported recently in the parotid glands of normal and streptozocin-diabetic Sprague-Dawley rats. The presence of an insulin-like material in the parotid salivary gland of two types of diabetic animals suggests that such cells may be spared, in part, from the effects of both chemical and hereditary diabetogenic factors.