By David N. Leff

Editor¿s note: Science Scan is a roundup of recently published biotechnology-related research.

Diabetes mellitus (DM) comes in two types, of which the second packs a paradox. Type I ¿ insulin dependent diabetes mellitus (IDDM) ¿ used to be called juvenile diabetes, because it usually strikes children. What it strikes them with is lack of insulin secreted in their pancreas, and a consequent disastrous rise in blood glucose. Individuals with Type II ¿ non-insulin dependent diabetes mellitus (NIDDM) make plenty of insulin, but their bodies resist that hormone¿s job of controlling glucose, so they too have hyperglycemia.

Two other salient differences between IDDM and NIDDM are age of onset and body weight. IDDM starts young; NIDDM kicks in after the age of 30. Its hallmark is obesity, and its preferred therapy is weight loss by diet and exercise.

When this patient-managed regimen fails, as it often does, physicians turn to two other treatment strategies. One is to overwhelm the insulin resistance with injections of more insulin. The other is to prescribe a drug that lowers glucose levels. Both have serious side effects, and both are medically controversial.

Now, Canadian diabetologists have come up with a potential drug target for treating Type II diabetes ¿ one that operates at the genetic and molecular levels. They report their candidate therapeutic in the issue of Science dated March 5, 1999. The article¿s title is ¿Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B [PTP-1B].¿

The co-authors had reason to suspect that PTP-1B, an enzyme, somehow reduces the ability of insulin to regulate blood glucose levels. To verify this suspicion, they constructed a strain of knockout mice lacking the gene that encodes the enzyme. Even when gorging on a high-fat, high-calorie diet, these perfectly healthy animals didn¿t gain much weight, and their insulin and glucose levels stayed on normal, even keels.

Specifically, their glucose concentrations were slightly lower than those of normal litter mates carrying the PTP-1B gene, and circulating insulin half that of those control mice. The latter, non-knockout cohort quickly put on excess weight and contracted NIDDM.

The paper cites findings suggesting that the enzyme works by turning off the receptor to which insulin molecules dock. It concludes that the results ¿make PTP-1B a potential therapeutic target for the treatment of Type II diabetes and obesity.¿

Hormonal Therapy In Rats Validates Pregnancy As Treatment Against Mammary Carcinomas

Our great-grandmothers knew that a woman¿s best protection against breast cancer was having a baby early in life. Oncologists today know that this old wives¿ maxim has a solid scientific basis.

One group of molecular oncologists at the University of California, in Berkeley, put it this way: ¿Women who have undergone a full-term pregnancy before 20 years of age have one-half the risk of developing breast cancer compared with nulliparous [never-pregnant] women. This protective effect of early pregnancy is universal, occurring among women of all ethnic groups worldwide.¿

That statement introduces a research paper in the March 2, 1999, issue of the Proceedings of the National Academy of Sciences. The article is titled: ¿Hormonal prevention of breast cancer: Mimicking the protective effect of pregnancy.¿

The authors made the point that this phenomenon ¿is clearly of major consideration in devising strategies for the prevention of breast cancer.¿ They report experiments in young virgin rats that point to the hormonal mechanism underlying pregnancy¿s protection against mammary carcinoma.

When a woman, or a rodent, becomes pregnant, many of her hormones go into action, preparing the mammary gland for lactation. Later, when the newborn finishes nursing and is weaned off its mother¿s milk, the lactogenic hormones go off-duty, and apoptosis reduces the milk-laden structures of the breast.

In a series of experiments on virginal and pregnant rats, the co-authors demonstrated that two hormones, estradiol and progesterone, which are very active during pregnancy, can abort the effects of mammary-targeting carcinogens.

Infants In Intense Malarial Areas Gain More Immunity Than Babies In Less-Extreme Zones

A typical article on development of a vaccine against malaria begins by pointing out that human malarial parasites cause 300 to 500 million illnesses and 1.5 to 3 million deaths worldwide, with children bearing the brunt of this morbidity and mortality. But the March 1999 issue of Nature Medicine carries a research paper titled ¿Immunity to non-cerebral severe malaria is acquired after one or two infections.¿ And an accompanying editorial is headed ¿Reducing malarial transmission may not be all good.¿

This contrarian data set cites ¿Experts [who have] long wondered why malaria morbidity is reduced in children in areas of high parasitic transmission.¿ One answer the paper puts forward is that infants while nursing are protected by the immune factors in their mothers¿ milk. And those in areas of intense transmission emerge with more of that immunity than babies in low-transmission regions.

The co-authors found that a single mosquito bite transmitting the Plasmodium falciparum parasite was sufficient to immunize a child in high-transmission situations, but low-transmission zones required three infections. Then, they made the counterintuitive point: ¿Interventions that reduce the force of infection, such as insecticide-treated bed-nets, may thus affect the disease rate adversely by raising the average [age] of first infection to beyond the period of post-natal protection.¿

The statement led one malaria expert cited in the editorial to warn, ¿Any vaccination program would still be a race against transmission, a race I am not sure we can win unless we can at the same time reduce transmissions.¿ n